Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T59480 Target Info
Target Name KRAS G12C mutant (KRAS G12C)
Target Type Successful Target
Gene Name KRAS
UniProt ID
RASK_HUMAN
Ligand General Information  Top
Ligand Name Guanosine-5'-Diphosphate Ligand Info
Canonical SMILES C1=NC2=C(N1C3C(C(C(O3)COP(=O)(O)OP(=O)(O)O)O)O)N=C(NC2=O)N
InChI 1S/C10H15N5O11P2/c11-10-13-7-4(8(18)14-10)12-2-15(7)9-6(17)5(16)3(25-9)1-24-28(22,23)26-27(19,20)21/h2-3,5-6,9,16-17H,1H2,(H,22,23)(H2,19,20,21)(H3,11,13,14,18)/t3-,5-,6-,9-/m1/s1
InChIKey QGWNDRXFNXRZMB-UUOKFMHZSA-N
PubChem Compound ID 135398619
Drug Binding Sites of Target  Top
PDB ID: 6PGP      Crystal structure of human KRAS G12C covalently bound to a quinazolinone inhibitor
Method X-ray diffraction Resolution 1.50 Å Mutation Yes [1]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKEK
Residue
Distance (Å)
ALA11
3.748
CYS12
3.853
GLY13
2.806
VAL14
3.320
GLY15
3.055
LYS16
2.836
SER17
3.018
ALA18
2.773
LEU19
4.988
PHE28
3.012
VAL29
3.328
ASP30
2.689
Residue
Distance (Å)
GLU31
4.881
TYR32
3.881
ASP57
4.759
ASN116
3.134
LYS117
3.023
SER118
4.749
ASP119
2.687
LEU120
3.508
THR144
4.666
SER145
3.343
ALA146
2.837
LYS147
3.388
PDB ID: 8DNI      Crystal structure of human KRAS G12C covalently bound with Araxes WO2020/028706A1 compound I-1
Method X-ray diffraction Resolution 1.50 Å Mutation Yes [2]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
LVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKSD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHKEK
169
Residue
Distance (Å)
ALA11
3.746
CYS12
3.946
GLY13
2.860
VAL14
3.338
GLY15
3.016
LYS16
2.735
SER17
2.917
ALA18
2.844
PHE28
3.427
VAL29
4.649
ASP30
2.831
GLU31
4.676
Residue
Distance (Å)
TYR32
4.010
PRO34
4.992
ASP57
4.537
ASN116
3.150
LYS117
3.155
SER118
4.845
ASP119
2.758
LEU120
3.444
THR144
4.714
SER145
3.420
ALA146
2.804
LYS147
3.314
PDB ID: 6PGO      Crystal structure of human KRAS G12C covalently bound to a phthalazine inhibitor
Method X-ray diffraction Resolution 1.60 Å Mutation Yes [1]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
RDQYMRTGEG
77
FLLVFAINNT
87
KSFEDIHHYR
97
EQIKRVKDSE
107

DVPMVLVGNK
117
SDLPSRTVDT
127
KQAQDLARSY
137
GIPFIETSAK
147
TRQGVDDAFY
157

TLVREIRKHK
167
Residue
Distance (Å)
ALA11
3.817
CYS12
3.840
GLY13
2.784
VAL14
3.358
GLY15
2.980
LYS16
2.768
SER17
2.986
ALA18
2.799
PHE28
3.308
VAL29
3.916
ASP30
2.741
GLU31
3.169
Residue
Distance (Å)
TYR32
3.688
PRO34
4.963
ASP57
4.644
ASN116
3.143
LYS117
3.074
SER118
4.821
ASP119
2.732
LEU120
3.287
THR144
4.806
SER145
3.449
ALA146
2.845
LYS147
3.338
PDB ID: 6OIM      Crystal Structure of human KRAS G12C covalently bound to AMG 510
Method X-ray diffraction Resolution 1.65 Å Mutation Yes [3]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
LVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDVPMV
112
LVGNKSDLPS
122
RTVDTKQAQD
132
LARSYGIPFI
142
ETSAKTRQGV
152

DDAFYTLVRE
162
IRKHKEK
Click to Show 3D Structure of This Binding Site
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Residue
Distance (Å)
ALA11
3.878
CYS12
3.961
GLY13
2.893
VAL14
3.423
GLY15
3.070
LYS16
2.789
SER17
2.985
ALA18
2.821
PHE28
3.390
VAL29
4.696
ASP30
2.838
GLU31
4.715
Residue
Distance (Å)
TYR32
3.894
PRO34
4.975
ASP57
4.532
ASN116
3.105
LYS117
3.112
SER118
4.785
ASP119
2.724
LEU120
3.437
THR144
4.743
SER145
3.390
ALA146
2.753
LYS147
3.398
PDB ID: 6P8Z      Crystal structure of human KRAS G12C covalently bound to an acryloylazetidine acetamide inhibitor
Method X-ray diffraction Resolution 1.65 Å Mutation Yes [4]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQAMRDQYMR
73
TGEGFLLVFA
83
INNTKSFEDI
93
HHYREQIKRV
103

KDSEDVPMVL
113
VGNKSDLPSR
123
TVDTKQAQDL
133
ARSYGIPFIE
143
TSAKTRQGVD
153

DAFYTLVREI
163
RKHKE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.722
CYS12
3.832
GLY13
2.758
VAL14
3.232
GLY15
2.953
LYS16
2.843
SER17
3.079
ALA18
2.811
PHE28
3.103
VAL29
3.002
ASP30
2.558
GLU31
4.139
Residue
Distance (Å)
TYR32
3.982
ASP57
4.706
ASN116
3.067
LYS117
3.093
SER118
4.703
ASP119
2.630
LEU120
3.386
THR144
4.509
SER145
3.300
ALA146
2.754
LYS147
3.486
PDB ID: 6P8W      Crystal structure of human KRAS G12C covalently bound to an acryloylazetidine acetamide inhibitor.
Method X-ray diffraction Resolution 2.10 Å Mutation Yes [4]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
LVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKSD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHKE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.893
CYS12
3.937
GLY13
2.816
VAL14
3.425
GLY15
3.035
LYS16
2.747
SER17
3.066
ALA18
2.860
PHE28
3.209
VAL29
3.557
ASP30
2.655
Residue
Distance (Å)
GLU31
4.574
TYR32
4.100
ASN116
3.109
LYS117
3.027
SER118
4.912
ASP119
2.809
LEU120
3.401
THR144
4.723
SER145
3.310
ALA146
2.708
LYS147
3.424
PDB ID: 6P8X      Crystal structure of human KRAS G12C covalently bound to an acryloylazetidine acetamide inhibitor.
Method X-ray diffraction Resolution 2.11 Å Mutation Yes [4]
PDB Sequence
TEYKLVVVGA
11
CGVGKSALTI
21
QLIQNHFVDE
31
YDPTIEDSYR
41
KQVVIDGETS
51

LLDILDTAGQ
61
EEYSAMRDQY
71
MRTGEGFLLV
81
FAINNTKSFE
91
DIHHYREQIK
101

RVKDSEDVPM
111
VLVGNKSDLP
121
SRTVDTKQAQ
131
DLARSYGIPF
141
IETSAKTRQG
151

VDDAFYTLVR
161
EIRKHK
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set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.858
CYS12
4.018
GLY13
2.982
VAL14
3.363
GLY15
3.075
LYS16
2.794
SER17
3.030
ALA18
2.864
PHE28
3.221
VAL29
2.906
ASP30
2.600
Residue
Distance (Å)
GLU31
4.799
TYR32
3.939
ASN116
3.108
LYS117
3.043
SER118
4.931
ASP119
2.756
LEU120
3.752
THR144
4.586
SER145
3.308
ALA146
2.655
LYS147
3.455
PDB ID: 6P8Y      Crystal structure of human KRAS G12C covalently bound to an acryloylazetidine acetamide inhibitor.
Method X-ray diffraction Resolution 2.31 Å Mutation Yes [4]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.836
CYS12
4.262
GLY13
3.239
VAL14
3.452
GLY15
3.141
LYS16
2.719
SER17
2.903
ALA18
2.771
PHE28
3.574
VAL29
4.477
TYR32
3.444
Residue
Distance (Å)
PRO34
4.923
ASP57
4.555
ASN116
3.304
LYS117
3.041
ASP119
2.922
LEU120
3.494
THR144
4.921
SER145
3.455
ALA146
2.767
LYS147
3.423
PDB ID: 7RP3      Crystal structure of GNE-1952 alkylated KRAS G12C in complex with 2H11 CLAMP
Method X-ray diffraction Resolution 2.00 Å Mutation Yes [5]
PDB Sequence
STEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKCDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.716
CYS12
3.796
GLY13
2.829
VAL14
3.508
GLY15
2.963
LYS16
2.509
SER17
2.941
ALA18
2.784
LEU19
4.939
PHE28
3.436
VAL29
2.929
ASP30
2.661
GLU31
3.897
Residue
Distance (Å)
TYR32
3.659
PRO34
4.774
ASP57
4.653
ASN116
3.004
LYS117
3.294
CYS118
4.773
ASP119
2.628
LEU120
3.740
THR144
4.613
SER145
3.215
ALA146
2.683
LYS147
3.439
PDB ID: 8AFB      CRYSTAL STRUCTURE OF KRAS-G12C IN COMPLEX WITH COMPOUND 23 (BI-0474)
Method X-ray diffraction Resolution 1.12 Å Mutation Yes [6]
PDB Sequence
TEYKLVVVGA
11
CGVGKSALTI
21
QLIQNHFVDE
31
YDPTIEDSYR
41
KQVVIDGETC
51

LLDILDTAGQ
61
EEYSAMRDQY
71
MRTGEGFLCV
81
FAINNTKSFE
91
DIHHYREQIK
101

RVKDSEDVPM
111
VLVGNKSDLP
121
SRTVDTKQAQ
131
DLARSYGIPF
141
IETSAKTRQG
151

VDDAFYTLVR
161
EIRK
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set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.830
CYS12
3.663
GLY13
2.764
VAL14
3.355
GLY15
3.006
LYS16
2.782
SER17
2.931
ALA18
2.887
PHE28
4.030
VAL29
4.969
ASP30
2.686
GLU31
4.674
Residue
Distance (Å)
TYR32
3.701
PRO34
4.645
ASP57
4.529
ASN116
3.221
LYS117
3.039
SER118
4.808
ASP119
2.796
LEU120
3.524
THR144
4.801
SER145
3.456
ALA146
2.813
LYS147
3.409
PDB ID: 4LDJ      Crystal Structure of a GDP-bound G12C Oncogenic Mutant of Human GTPase KRas
Method X-ray diffraction Resolution 1.15 Å Mutation Yes [7]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TCLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
CVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKCD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHKEK
169
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147 or .A:148; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.824
CYS12
3.124
GLY13
1.952
VAL14
2.799
GLY15
2.235
LYS16
1.931
SER17
2.136
ALA18
2.065
LEU19
4.599
PHE28
3.126
VAL29
4.337
ASP30
1.865
GLU31
3.858
Residue
Distance (Å)
TYR32
3.670
PRO34
3.941
ASP57
4.572
ASN116
2.429
LYS117
2.568
CYS118
4.569
ASP119
1.924
LEU120
2.488
THR144
4.644
SER145
2.768
ALA146
2.273
LYS147
2.643
THR148
4.997
PDB ID: 6TAN      X-RAY STRUCTURE OF HUMAN K-RAS G12C IN COMPLEX WITH COVALENT ISOQUINOLINONE INHIBITOR (COMPOUND 17)
Method X-ray diffraction Resolution 1.16 Å Mutation Yes [8]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
LVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKSD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHKEK
169
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.919
CYS12
3.880
GLY13
2.840
VAL14
3.349
GLY15
3.041
LYS16
2.787
SER17
2.941
ALA18
2.853
PHE28
3.592
VAL29
4.731
ASP30
2.767
GLU31
4.707
Residue
Distance (Å)
TYR32
3.962
PRO34
4.979
ASP57
4.452
ASN116
3.151
LYS117
3.100
SER118
4.733
ASP119
2.810
LEU120
3.439
THR144
4.760
SER145
3.496
ALA146
2.848
LYS147
3.385
PDB ID: 7O70      KRasG12C ligand complex
Method X-ray diffraction Resolution 1.18 Å Mutation Yes [9]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
LVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKSD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.770
CYS12
3.877
GLY13
2.840
VAL14
3.345
GLY15
3.072
LYS16
2.811
SER17
3.070
ALA18
2.761
LEU19
4.993
PHE28
3.125
VAL29
2.881
ASP30
2.699
GLU31
4.716
Residue
Distance (Å)
TYR32
3.884
PRO34
4.998
ASP57
4.674
ASN116
3.089
LYS117
3.064
SER118
4.734
ASP119
2.757
LEU120
3.459
THR144
4.647
SER145
3.398
ALA146
2.862
LYS147
3.429
PDB ID: 7R0N      KRasG12C in complex with GDP and compound 2
Method X-ray diffraction Resolution 1.20 Å Mutation Yes [10]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
LVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDVPMV
112
LVGNKSDLPS
122
RTVDTKQAQD
132
LARSYGIPFI
142
ETSAKTRQGV
152

DDAFYTLVRE
162
IRKHKEK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.844
CYS12
3.946
GLY13
2.860
VAL14
3.388
GLY15
3.088
LYS16
2.785
SER17
3.019
ALA18
2.852
PHE28
3.520
VAL29
4.851
ASP30
2.791
GLU31
4.767
Residue
Distance (Å)
TYR32
3.962
PRO34
4.793
ASP57
4.508
ASN116
3.219
LYS117
3.088
SER118
4.830
ASP119
2.803
LEU120
3.561
THR144
4.795
SER145
3.531
ALA146
2.817
LYS147
3.378
PDB ID: 4LUC      Crystal Structure of small molecule disulfide 6 bound to K-Ras G12C
Method X-ray diffraction Resolution 1.29 Å Mutation Yes [11]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147 or .A:148; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.793
CYS12
3.502
GLY13
2.026
VAL14
2.794
GLY15
2.241
LYS16
2.000
SER17
2.179
ALA18
1.934
LEU19
4.449
PHE28
2.709
VAL29
2.241
ASP30
1.867
GLU31
3.803
Residue
Distance (Å)
TYR32
3.504
PRO34
4.401
ASP57
4.705
ASN116
2.381
LYS117
2.561
SER118
4.351
ASP119
1.811
LEU120
2.501
THR144
4.606
SER145
2.625
ALA146
2.175
LYS147
2.700
THR148
4.893
PDB ID: 6B0V      Crystal Structure of small molecule ARS-107 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.29 Å Mutation Yes [12]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.806
CYS12
3.804
GLY13
2.745
VAL14
3.344
GLY15
3.022
LYS16
2.759
SER17
2.982
ALA18
2.760
PHE28
3.072
VAL29
2.876
ASP30
2.786
GLU31
4.823
Residue
Distance (Å)
TYR32
4.093
ASP57
4.732
ASN116
3.105
LYS117
3.088
SER118
4.792
ASP119
2.794
LEU120
3.495
THR144
4.714
SER145
3.414
ALA146
2.897
LYS147
3.398
PDB ID: 7A1X      KRASG12C GDP form in complex with Cpd1
Method X-ray diffraction Resolution 1.32 Å Mutation Yes [13]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TCLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
CVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKCD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHKEK
169
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.831
CYS12
3.759
GLY13
2.784
VAL14
3.343
GLY15
2.995
LYS16
2.779
SER17
2.950
ALA18
2.853
PHE28
3.808
VAL29
4.777
ASP30
2.670
GLU31
4.594
Residue
Distance (Å)
TYR32
3.672
PRO34
4.602
ASP57
4.592
ASN116
3.142
LYS117
3.035
CYS118
4.924
ASP119
2.803
LEU120
3.534
THR144
4.670
SER145
3.480
ALA146
2.824
LYS147
3.348
PDB ID: 4LYH      Crystal Structure of small molecule vinylsulfonamide 9 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.37 Å Mutation Yes [11]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
IEDSYRKQVV
45
IDGETSLLDI
55

LDTAGQEEYS
65
AMRDQYMRTG
75
EGFLLVFAIN
85
NTKSFEDIHH
95
YREQIKRVKD
105

SEDVPMVLVG
115
NKSDLPSRTV
125
DTKQAQDLAR
135
SYGIPFIETS
145
AKTRQGVDDA
155

FYTLVREIRK
165
HKE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:36 or .A:38 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147 or .A:148; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.770
CYS12
3.162
GLY13
1.946
VAL14
2.881
GLY15
2.276
LYS16
1.918
SER17
2.094
ALA18
2.096
LEU19
4.689
PHE28
2.952
VAL29
2.942
ASP30
2.330
ILE36
4.981
Residue
Distance (Å)
ASP38
4.734
ASP57
4.678
ASN116
2.504
LYS117
2.548
SER118
4.449
ASP119
1.806
LEU120
2.390
THR144
4.645
SER145
2.670
ALA146
2.250
LYS147
2.884
THR148
4.985
PDB ID: 6T5B      KRasG12C ligand complex
Method X-ray diffraction Resolution 1.37 Å Mutation Yes [14]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
LVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKSD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
IREIRKHKEK
169
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.753
CYS12
3.906
GLY13
2.888
VAL14
3.286
GLY15
2.947
LYS16
2.809
SER17
2.996
ALA18
2.761
PHE28
3.574
VAL29
4.513
ASP30
3.107
GLU31
2.888
Residue
Distance (Å)
TYR32
3.513
PRO34
4.629
ASP57
4.599
ASN116
3.179
LYS117
3.041
SER118
4.758
ASP119
2.758
LEU120
3.535
THR144
4.625
SER145
3.414
ALA146
2.780
LYS147
3.617
PDB ID: 5V9U      Crystal Structure of small molecule ARS-1620 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.38 Å Mutation Yes [15]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKEK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.747
CYS12
3.824
GLY13
2.809
VAL14
3.245
GLY15
2.949
LYS16
2.793
SER17
3.009
ALA18
2.819
PHE28
3.227
VAL29
2.749
ASP30
2.699
GLU31
4.301
Residue
Distance (Å)
TYR32
4.033
PRO34
4.991
ASP57
4.811
ASN116
3.077
LYS117
3.142
SER118
4.800
ASP119
2.697
LEU120
3.559
THR144
4.617
SER145
3.452
ALA146
2.871
LYS147
3.464
PDB ID: 5F2E      Crystal Structure of small molecule ARS-853 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.40 Å Mutation Yes [16]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
LVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKSD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.722
CYS12
3.846
GLY13
2.771
VAL14
3.306
GLY15
2.986
LYS16
2.761
SER17
2.941
ALA18
2.871
PHE28
3.112
VAL29
3.268
ASP30
2.924
GLU31
4.674
Residue
Distance (Å)
TYR32
3.853
PRO34
4.818
ASP57
4.567
ASN116
3.153
LYS117
3.144
SER118
4.779
ASP119
2.803
LEU120
3.479
THR144
4.631
SER145
3.476
ALA146
2.852
LYS147
3.489
PDB ID: 6B0Y      Crystal Structure of small molecule ARS-917 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.43 Å Mutation Yes [12]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.747
CYS12
3.821
GLY13
2.810
VAL14
3.212
GLY15
2.966
LYS16
2.820
SER17
2.979
ALA18
2.793
PHE28
3.198
VAL29
2.873
ASP30
2.733
GLU31
4.459
Residue
Distance (Å)
TYR32
4.061
PRO34
4.996
ASP57
4.805
ASN116
3.092
LYS117
3.129
SER118
4.809
ASP119
2.738
LEU120
3.621
THR144
4.649
SER145
3.386
ALA146
2.866
LYS147
3.454
PDB ID: 4M1Y      Crystal Structure of small molecule vinylsulfonamide 15 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.49 Å Mutation Yes [11]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EEDSYRKQVV
45
IDGETSLLDI
55

LDTAGEEYSA
66
MRDQYMRTGE
76
GFLLVFAINN
86
TKSFEDIHHY
96
REQIKRVKDS
106

EDVPMVLVGN
116
KSDLPSRTVD
126
TKQAQDLARS
136
YGIPFIETSA
146
KTRQGVDDAF
156

YTLVREIRKH
166
KE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147 or .A:148; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.837
CYS12
3.220
GLY13
1.980
VAL14
2.880
GLY15
2.188
LYS16
1.870
SER17
2.098
ALA18
2.064
LEU19
4.651
PHE28
2.970
VAL29
2.769
ASP30
2.527
Residue
Distance (Å)
GLU31
3.463
ASP57
4.655
ASN116
2.451
LYS117
2.594
SER118
4.469
ASP119
1.908
LEU120
2.418
THR144
4.663
SER145
2.630
ALA146
2.179
LYS147
2.847
THR148
4.971
PDB ID: 4LV6      Crystal Structure of small molecule disulfide 4 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.50 Å Mutation Yes [11]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147 or .A:148; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.719
CYS12
3.504
GLY13
2.074
VAL14
2.822
GLY15
2.229
LYS16
1.883
SER17
2.216
ALA18
1.977
LEU19
4.546
PHE28
2.746
VAL29
2.486
ASP30
1.840
GLU31
3.831
Residue
Distance (Å)
TYR32
3.404
PRO34
4.433
ASP57
4.581
ASN116
2.399
LYS117
2.611
SER118
4.447
ASP119
1.940
LEU120
2.539
THR144
4.701
SER145
2.648
ALA146
2.263
LYS147
2.637
THR148
4.932
PDB ID: 4L8G      Crystal Structure of K-Ras G12C, GDP-bound
Method X-ray diffraction Resolution 1.52 Å Mutation Yes [11]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHHYREQI
100
KRVKDSEDVP
110

MVLVGNKCDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150
GVDDAFYTLV
160

REIRKHK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147 or .A:148; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.784
CYS12
3.032
GLY13
1.971
VAL14
2.759
GLY15
2.278
LYS16
1.916
SER17
2.141
ALA18
2.046
LEU19
4.564
PHE28
2.765
VAL29
2.149
ASP30
1.871
GLU31
2.825
Residue
Distance (Å)
TYR32
3.252
PRO34
4.126
ASP57
4.764
ASN116
2.372
LYS117
2.556
CYS118
4.485
ASP119
1.815
LEU120
2.461
THR144
4.635
SER145
2.644
ALA146
2.374
LYS147
2.727
THR148
4.919
PDB ID: 4M1S      Crystal Structure of small molecule vinylsulfonamide 13 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.55 Å Mutation Yes [11]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EDSYRKQVVI
46
DGETSLLDIL
56

DTAGQEEYSA
66
MRDQYMRTGE
76
GFLLVFAINN
86
TKSFEDIHHY
96
REQIKRVKDS
106

EDVPMVLVGN
116
KSDLPSRTVD
126
TKQAQDLARS
136
YGIPFIETSA
146
KTRQGVDDAF
156

YTLVREIRKH
166
K
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.854
CYS12
3.231
GLY13
1.967
VAL14
2.881
GLY15
2.231
LYS16
1.962
SER17
2.065
ALA18
2.025
LEU19
4.693
PHE28
3.015
VAL29
3.078
Residue
Distance (Å)
ASP30
2.413
ASP57
4.601
ASN116
2.444
LYS117
2.591
SER118
4.464
ASP119
1.922
LEU120
2.382
THR144
4.711
SER145
2.637
ALA146
2.172
LYS147
2.876
PDB ID: 4LYF      Crystal Structure of small molecule vinylsulfonamide 8 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.57 Å Mutation Yes [11]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EDSYRKQVVI
46
DGETSLLDIL
56

DTAGQEEYSA
66
MRDQYMRTGE
76
GFLLVFAINN
86
TKSFEDIHHY
96
REQIKRVKDS
106

EDVPMVLVGN
116
KSDLPSRTVD
126
TKQAQDLARS
136
YGIPFIETSA
146
KTRQGVDDAF
156

YTLVREIRKH
166
K
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:38 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.864
CYS12
3.271
GLY13
1.988
VAL14
2.862
GLY15
2.210
LYS16
1.904
SER17
2.124
ALA18
2.052
LEU19
4.676
PHE28
2.951
VAL29
2.892
ASP30
2.757
Residue
Distance (Å)
ASP38
4.878
ASP57
4.620
ASN116
2.460
LYS117
2.587
SER118
4.488
ASP119
1.906
LEU120
2.426
THR144
4.701
SER145
2.673
ALA146
2.205
LYS147
2.924
PDB ID: 4M1O      Crystal Structure of small molecule vinylsulfonamide 7 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.57 Å Mutation Yes [11]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EDSYRKQVVI
46
DGETSLLDIL
56

DTAGQEEYSA
66
MRDQYMRTGE
76
GFLLVFAINN
86
TKSFEDIHHY
96
REQIKRVKDS
106

EDVPMVLVGN
116
KSDLPSRTVD
126
TKQAQDLARS
136
YGIPFIETSA
146
KTRQGVDDAF
156

YTLVREIRKH
166
K
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.845
CYS12
3.226
GLY13
1.969
VAL14
2.919
GLY15
2.214
LYS16
1.899
SER17
2.054
ALA18
2.084
LEU19
4.670
PHE28
3.006
VAL29
2.953
Residue
Distance (Å)
ASP30
2.338
ASP57
4.632
ASN116
2.439
LYS117
2.551
SER118
4.519
ASP119
1.961
LEU120
2.558
THR144
4.683
SER145
2.695
ALA146
2.206
LYS147
2.912
PDB ID: 4M1W      Crystal Structure of small molecule vinylsulfonamide covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.58 Å Mutation Yes [11]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EDSYRKQVVI
46
DGETSLLDIL
56

DTAGQESAMR
68
DQYMRTGEGF
78
LLVFAINNTK
88
SFEDIHHYRE
98
QIKRVKDSED
108

VPMVLVGNKS
118
DLPSRTVDTK
128
QAQDLARSYG
138
IPFIETSAKT
148
RQGVDDAFYT
158

LVREIRKHKE
168
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147 or .A:148; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.865
CYS12
3.147
GLY13
1.971
VAL14
2.911
GLY15
2.216
LYS16
1.943
SER17
2.052
ALA18
2.018
LEU19
4.672
PHE28
2.993
VAL29
2.959
ASP30
2.512
Residue
Distance (Å)
ASP57
4.592
ASN116
2.413
LYS117
2.599
SER118
4.498
ASP119
1.952
LEU120
2.467
THR144
4.701
SER145
2.685
ALA146
2.191
LYS147
2.832
THR148
4.988
PDB ID: 7R0M      KRasG12C in complex with GDP and JDQ443
Method X-ray diffraction Resolution 1.61 Å Mutation Yes [10]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.676
CYS12
3.812
GLY13
2.812
VAL14
3.201
GLY15
2.996
LYS16
2.830
SER17
3.086
ALA18
2.852
PHE28
3.116
VAL29
3.412
ASP30
2.752
GLU31
3.846
Residue
Distance (Å)
TYR32
3.889
ASP57
4.708
ASN116
3.140
LYS117
3.147
SER118
4.843
ASP119
2.788
LEU120
3.532
THR144
4.737
SER145
3.443
ALA146
2.837
LYS147
3.413
PDB ID: 6TAM      X-RAY STRUCTURE OF HUMAN K-RAS G12C IN COMPLEX WITH COVALENT ISOQUINOLINONE INHIBITOR (COMPOUND 3)
Method X-ray diffraction Resolution 1.64 Å Mutation Yes [8]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
LVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKSD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHKEK
169
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.813
CYS12
3.915
GLY13
2.871
VAL14
3.350
GLY15
3.051
LYS16
2.772
SER17
3.006
ALA18
2.839
PHE28
3.426
VAL29
4.740
ASP30
2.783
GLU31
4.706
Residue
Distance (Å)
TYR32
3.933
PRO34
4.957
ASP57
4.467
ASN116
3.123
LYS117
3.062
SER118
4.778
ASP119
2.791
LEU120
3.471
THR144
4.786
SER145
3.476
ALA146
2.864
LYS147
3.410
PDB ID: 5YY1      Co-crystal Structure of KRAS (G12C) covalently bound with Quinazoline based inhibitor JBI739
Method X-ray diffraction Resolution 1.69 Å Mutation Yes [17]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
LVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKSD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHKEK
169
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.750
CYS12
3.811
GLY13
2.802
VAL14
3.389
GLY15
2.997
LYS16
2.736
SER17
3.018
ALA18
2.782
PHE28
3.278
VAL29
3.532
ASP30
2.719
GLU31
4.584
Residue
Distance (Å)
TYR32
3.739
ASP57
4.607
ASN116
3.105
LYS117
3.154
SER118
4.752
ASP119
2.800
LEU120
3.450
THR144
4.697
SER145
3.354
ALA146
2.764
LYS147
3.364
PDB ID: 4M1T      Crystal Structure of small molecule vinylsulfonamide 14 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.70 Å Mutation Yes [11]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
IEDSYRKQVV
45
IDGETSLLDI
55

LDTAGQEEYS
65
AMRDQYMRTG
75
EGFLLVFAIN
85
NTKSFEDIHH
95
YREQIKRVKD
105

SEDVPMVLVG
115
NKSDLPSRTV
125
DTKQAQDLAR
135
SYGIPFIETS
145
AKTRQGVDDA
155

FYTLVREIRK
165
HKE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147 or .A:148; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.909
CYS12
3.228
GLY13
2.036
VAL14
2.848
GLY15
2.212
LYS16
1.880
SER17
2.105
ALA18
2.053
LEU19
4.631
PHE28
3.010
VAL29
3.616
ASP30
2.606
Residue
Distance (Å)
ASP57
4.669
ASN116
2.436
LYS117
2.566
SER118
4.488
ASP119
1.997
LEU120
2.474
THR144
4.679
SER145
2.651
ALA146
2.198
LYS147
2.876
THR148
4.970
PDB ID: 5V6S      Crystal structure of small molecule acrylamide 1 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.70 Å Mutation Yes [18]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
LVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKSD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHKEK
169
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147 or .A:148; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.854
CYS12
3.350
GLY13
1.999
VAL14
3.002
GLY15
2.317
LYS16
1.912
SER17
2.246
ALA18
2.044
LEU19
4.562
PHE28
2.645
VAL29
2.122
ASP30
2.312
GLU31
3.822
Residue
Distance (Å)
TYR32
3.910
PRO34
4.246
ASP57
4.562
ASN116
2.530
LYS117
2.531
SER118
4.463
ASP119
1.744
LEU120
2.284
THR144
4.668
SER145
2.629
ALA146
2.218
LYS147
2.709
THR148
4.864
PDB ID: 5YXZ      Co-crystal Structure of KRAS (G12C) covalently bound with Quinazoline based inhibitor JBI484
Method X-ray diffraction Resolution 1.70 Å Mutation Yes [19]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
LVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKSD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHKEK
169
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.838
CYS12
3.901
GLY13
2.832
VAL14
3.331
GLY15
3.024
LYS16
2.733
SER17
3.027
ALA18
2.759
PHE28
3.436
VAL29
3.842
ASP30
2.961
GLU31
4.666
Residue
Distance (Å)
TYR32
3.888
PRO34
4.808
ASP57
4.594
ASN116
3.068
LYS117
3.174
SER118
4.734
ASP119
2.707
LEU120
3.430
THR144
4.636
SER145
3.397
ALA146
2.762
LYS147
3.483
PDB ID: 5V6V      Crystal structure of small molecule aziridine 3 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.72 Å Mutation Yes [18]
PDB Sequence
TEYKLVVVGA
11
CGVGKSALTI
21
QLIQNHFVDE
31
YDPTIEDSYR
41
KQVVIDGETS
51

LLDILDTAGQ
61
EEYSAMRDQY
71
MRTGEGFLLV
81
FAINNTKSFE
91
DIHHYREQIK
101

RVKDSEDVPM
111
VLVGNKSDLP
121
SRTVDTKQAQ
131
DLARSYGIPF
141
IETSAKTRQG
151

VDDAFYTLVR
161
EIRKHK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147 or .A:148; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.803
CYS12
3.455
GLY13
2.003
VAL14
2.815
GLY15
2.212
LYS16
1.858
SER17
2.160
ALA18
2.103
LEU19
4.649
PHE28
2.250
VAL29
2.964
ASP30
2.105
GLU31
2.250
Residue
Distance (Å)
TYR32
3.589
PRO34
4.424
ASP57
4.719
ASN116
2.426
LYS117
2.506
SER118
4.479
ASP119
1.779
LEU120
2.453
THR144
4.691
SER145
2.599
ALA146
2.221
LYS147
2.656
THR148
4.900
PDB ID: 6N2K      Tetrahydropyridopyrimidines as Covalent Inhibitors of KRAS-G12C
Method X-ray diffraction Resolution 1.72 Å Mutation Yes [20]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKEK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.773
CYS12
3.846
GLY13
2.830
VAL14
3.280
GLY15
3.012
LYS16
2.791
SER17
2.939
ALA18
2.789
PHE28
3.199
VAL29
2.735
ASP30
2.631
GLU31
4.503
Residue
Distance (Å)
TYR32
3.718
PRO34
4.822
ASP57
4.559
ASN116
3.124
LYS117
3.143
SER118
4.642
ASP119
2.766
LEU120
3.460
THR144
4.570
SER145
3.286
ALA146
2.834
LYS147
3.614
PDB ID: 6ARK      Crystal Structure of compound 10 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.75 Å Mutation Yes [21]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQEMRDQYMR
73
TGEGFLLVFA
83
INNTKSFEDI
93
HHYREQIKRV
103

KDSEDVPMVL
113
VGNKSDLPSR
123
TVDTKQAQDL
133
ARSYGIPFIE
143
TSAKTRQGVD
153

DAFYTLVREI
163
RKHKEK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147 or .A:148; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.810
CYS12
3.233
GLY13
2.040
VAL14
2.889
GLY15
2.119
LYS16
1.678
SER17
2.091
ALA18
2.111
LEU19
4.773
PHE28
2.249
VAL29
2.666
ASP30
2.429
GLU31
3.424
Residue
Distance (Å)
TYR32
3.598
PRO34
4.641
ASP57
4.465
ASN116
2.407
LYS117
2.553
SER118
4.483
ASP119
1.737
LEU120
2.220
THR144
4.801
SER145
2.637
ALA146
2.148
LYS147
2.783
THR148
4.998
PDB ID: 7A1W      KRASG12C GDP form in complex with Cpd3
Method X-ray diffraction Resolution 1.76 Å Mutation Yes [13]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKCDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.926
CYS12
3.749
GLY13
2.769
VAL14
3.466
GLY15
3.085
LYS16
2.706
SER17
2.975
ALA18
2.832
PHE28
3.241
VAL29
2.865
ASP30
2.828
GLU31
4.362
Residue
Distance (Å)
TYR32
3.939
PRO34
4.685
ASP57
4.610
ASN116
3.093
LYS117
3.189
CYS118
4.790
ASP119
2.793
LEU120
3.518
THR144
4.592
SER145
3.403
ALA146
2.805
LYS147
3.552
PDB ID: 7YCC      KRas G12C in complex with Compound 5c
Method X-ray diffraction Resolution 1.79 Å Mutation Yes [22]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEMRDQYMRT
74
GEGFLCVFAI
84
NNTKSFEDIH
94
HYREQIKRVK
104

DSEDVPMVLV
114
GNKSDLPSRT
124
VDTKQAQDLA
134
RSYGIPFIET
144
SAKTRQGVDD
154

AFYTLVREIR
164
KHKEK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.612
CYS12
3.738
GLY13
2.694
VAL14
3.454
GLY15
3.087
LYS16
2.498
SER17
2.966
ALA18
2.618
LEU19
4.908
PHE28
3.441
VAL29
3.120
ASP30
2.711
Residue
Distance (Å)
GLU31
4.255
TYR32
3.771
ASP57
4.593
ASN116
3.200
LYS117
3.071
SER118
4.716
ASP119
2.851
LEU120
3.423
THR144
4.707
SER145
3.464
ALA146
2.865
LYS147
3.402
PDB ID: 6N2J      Tetrahydropyridopyrimidines as Covalent Inhibitors of KRAS-G12C
Method X-ray diffraction Resolution 1.80 Å Mutation Yes [20]
PDB Sequence
TEYKLVVVGA
11
CGVGKSALTI
21
QLIQNHFVDE
31
YDPTIEDSYR
41
KQVVIDGETS
51

LLDILDTAGQ
61
EEYSAMRDQY
71
MRTGEGFLLV
81
FAINNTKSFE
91
DIHHYREQIK
101

RVKDSEDVPM
111
VLVGNKSDLP
121
SRTVDTKQAQ
131
DLARSYGIPF
141
IETSAKTRQG
151

VDDAFYTLVR
161
EIRKHKEK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.698
CYS12
3.730
GLY13
2.737
VAL14
3.320
GLY15
3.073
LYS16
2.794
SER17
2.990
ALA18
2.797
PHE28
3.232
VAL29
3.030
ASP30
2.682
GLU31
4.391
Residue
Distance (Å)
TYR32
3.714
ASP57
4.566
ASN116
3.082
LYS117
3.214
SER118
4.714
ASP119
2.779
LEU120
3.419
THR144
4.680
SER145
3.385
ALA146
2.907
LYS147
3.515
PDB ID: 7YCE      KRas G12C in complex with Compound 7b
Method X-ray diffraction Resolution 1.80 Å Mutation Yes [22]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKEK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.759
CYS12
3.812
GLY13
2.803
VAL14
3.427
GLY15
3.002
LYS16
2.731
SER17
2.933
ALA18
2.707
LEU19
4.956
PHE28
3.539
VAL29
3.052
ASP30
2.732
Residue
Distance (Å)
GLU31
4.408
TYR32
3.750
ASP57
4.597
ASN116
3.113
LYS117
3.045
SER118
4.807
ASP119
2.818
LEU120
3.545
THR144
4.781
SER145
3.452
ALA146
2.877
LYS147
3.333
PDB ID: 4LYJ      Crystal Structure of small molecule vinylsulfonamide 9 covalently bound to K-Ras G12C, alternative space group
Method X-ray diffraction Resolution 1.93 Å Mutation Yes [11]
PDB Sequence
TEYKLVVVGA
11
CGVGKSALTI
21
QLIQNHFVDE
31
YDPTIEDSYR
41
KQVVIDGETS
51

LLDILDTAGQ
61
EEYSAMRDQY
71
MRTGEGFLLV
81
FAINNTKSFE
91
DIHHYREQIK
101

RVKDSEDVPM
111
VLVGNKSDLP
121
SRTVDTKQAQ
131
DLARSYGIPF
141
IETSAKTRQG
151

VDDAFYTLVR
161
EIRKHK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:62 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.699
CYS12
4.012
GLY13
2.951
VAL14
3.289
GLY15
3.091
LYS16
2.656
SER17
2.950
ALA18
2.893
PHE28
3.397
VAL29
2.891
ASP30
2.969
GLU31
4.807
Residue
Distance (Å)
TYR32
2.614
GLU62
4.662
ASN116
3.147
LYS117
3.337
SER118
4.771
ASP119
2.794
LEU120
3.356
THR144
4.658
SER145
3.418
ALA146
2.822
LYS147
3.582
PDB ID: 4M21      Crystal Structure of small molecule acrylamide 11 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 1.94 Å Mutation Yes [11]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
IEDSYRKQVV
45
IDGETSLLDI
55

LDTAGQSAMR
68
DQYMRTGEGF
78
LLVFAINNTK
88
SFEDIHHYRE
98
QIKRVKDSED
108

VPMVLVGNKS
118
DLPSRTVDTK
128
QAQDLARSYG
138
IPFIETSAKT
148
RQGVDDAFYT
158

LVREIRKHK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147 or .A:148; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.880
CYS12
3.316
GLY13
2.064
VAL14
2.895
GLY15
2.280
LYS16
1.809
SER17
2.134
ALA18
2.132
LEU19
4.738
PHE28
3.016
VAL29
3.072
ASP30
2.665
Residue
Distance (Å)
ASP57
4.703
ASN116
2.421
LYS117
2.682
SER118
4.502
ASP119
2.053
LEU120
2.608
THR144
4.831
SER145
2.697
ALA146
2.132
LYS147
2.720
THR148
4.975
PDB ID: 6UT0      Identification of the Clinical Development Candidate MRTX849, a Covalent KRASG12C Inhibitor for the Treatment of Cancer
Method X-ray diffraction Resolution 1.94 Å Mutation Yes [23]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKEK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147 or .A:148; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.710
CYS12
3.107
GLY13
1.917
VAL14
2.865
GLY15
2.281
LYS16
1.773
SER17
2.188
ALA18
1.988
LEU19
4.420
PHE28
2.666
VAL29
3.961
ASP30
1.720
GLU31
3.642
Residue
Distance (Å)
TYR32
3.826
PRO34
4.093
ASP57
4.636
ASN116
2.475
LYS117
2.542
SER118
4.528
ASP119
1.830
LEU120
2.415
THR144
4.837
SER145
2.766
ALA146
2.275
LYS147
2.544
THR148
4.815
PDB ID: 7R0Q      KRasG12C in complex with GDP and compound 3
Method X-ray diffraction Resolution 1.95 Å Mutation Yes [10]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.627
CYS12
3.999
GLY13
2.965
VAL14
3.135
GLY15
3.088
LYS16
2.648
SER17
3.015
ALA18
2.879
PHE28
3.341
VAL29
3.640
ASP30
2.683
GLU31
4.895
Residue
Distance (Å)
TYR32
3.777
ASP57
4.628
ASN116
3.245
LYS117
3.165
SER118
4.917
ASP119
2.828
LEU120
3.670
THR144
4.744
SER145
3.407
ALA146
2.815
LYS147
3.384
PDB ID: 7A1Y      KRASG12C GDP form in complex with Cpd2
Method X-ray diffraction Resolution 2.00 Å Mutation Yes [13]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEEYMRDQYM
72
RTGEGFLCVF
82
AINNTKSFED
92
IHHYREQIKR
102

VKDSEDVPMV
112
LVGNKCDLPS
122
RTVDTKQAQD
132
LARSYGIPFI
142
ETSAKTRQGV
152

DDAFYTLVRE
162
IRKHKEK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.836
CYS12
3.791
GLY13
2.841
VAL14
3.403
GLY15
3.093
LYS16
2.790
SER17
2.991
ALA18
2.853
PHE28
3.292
VAL29
2.593
ASP30
2.606
GLU31
4.146
Residue
Distance (Å)
TYR32
3.669
PRO34
4.956
ASP57
4.576
ASN116
2.996
LYS117
3.190
CYS118
4.879
ASP119
2.894
LEU120
3.487
THR144
4.640
SER145
3.454
ALA146
2.807
LYS147
3.533
PDB ID: 6USZ      Identification of the Clinical Development Candidate MRTX849, a Covalent KRASG12C Inhibitor for the Treatment of Cancer
Method X-ray diffraction Resolution 2.03 Å Mutation Yes [23]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKEK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.729
CYS12
3.801
GLY13
2.825
VAL14
3.389
GLY15
3.093
LYS16
2.637
SER17
2.944
ALA18
2.821
PHE28
3.194
VAL29
3.198
ASP30
2.666
GLU31
4.584
Residue
Distance (Å)
TYR32
3.780
PRO34
4.915
ASP57
4.573
ASN116
3.179
LYS117
2.987
SER118
4.780
ASP119
2.714
LEU120
3.422
THR144
4.699
SER145
3.391
ALA146
2.819
LYS147
3.519
PDB ID: 4M22      Crystal Structure of small molecule acrylamide 16 covalently bound to K-Ras G12C
Method X-ray diffraction Resolution 2.09 Å Mutation Yes [11]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAR
68
DQYMRTGEGF
78
LLVFAINNTK
88
SFEDIHHYRE
98
QIKRVKDSED
108

VPMVLVGNKS
118
DLPSRTVDTK
128
QAQDLARSYG
138
IPFIETSAKT
148
RQGVDDAFYT
158

LVREIRKHKE
168
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147 or .A:148; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.875
CYS12
3.132
GLY13
1.923
VAL14
2.901
GLY15
2.234
LYS16
1.869
SER17
2.204
ALA18
2.102
LEU19
4.581
PHE28
2.903
VAL29
2.729
ASP30
2.199
GLU31
3.503
Residue
Distance (Å)
TYR32
3.531
PRO34
3.985
ASP57
4.531
ASN116
2.497
LYS117
2.556
SER118
4.400
ASP119
2.033
LEU120
2.519
THR144
4.800
SER145
2.714
ALA146
2.306
LYS147
2.633
THR148
4.973
PDB ID: 4LRW      Crystal Structure of K-Ras G12C (cysteine-light), GDP-bound
Method X-ray diffraction Resolution 2.15 Å Mutation Yes [11]
PDB Sequence
TEYKLVVVGA
11
CGVGKSALTI
21
QLIQNHFVDE
31
YDPTIEDSYR
41
KQVVIDGETS
51

LLDILDTAYM
72
RTGEGFLLVF
82
AINNTKSFED
92
IHHYREQIKR
102
VKDSEDVPMV
112

LVGNKSDLPS
122
RTVDTKQAQD
132
LARSYGIPFI
142
ETSAKTRQGV
152
DDAFYTLVRE
162

IRKHK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.966
CYS12
3.612
GLY13
2.648
VAL14
3.491
GLY15
3.004
LYS16
2.663
SER17
3.012
ALA18
2.927
PHE28
3.182
VAL29
3.085
ASP30
2.395
GLU31
3.468
Residue
Distance (Å)
TYR32
3.594
ASP57
4.797
ASN116
3.094
LYS117
3.368
SER118
4.740
ASP119
2.405
LEU120
3.423
THR144
4.535
SER145
3.279
ALA146
2.817
LYS147
3.592
PDB ID: 7RP4      Crystal structure of KRAS G12C in complex with GNE-1952
Method X-ray diffraction Resolution 2.15 Å Mutation Yes [5]
PDB Sequence
STEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKEK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.594
CYS12
4.105
GLY13
3.053
VAL14
3.545
GLY15
2.993
LYS16
2.562
SER17
2.850
ALA18
2.720
PHE28
3.152
VAL29
3.301
ASP30
2.273
GLU31
4.190
Residue
Distance (Å)
TYR32
4.000
PRO34
4.901
ASP57
4.628
ASN116
3.221
LYS117
3.351
SER118
4.762
ASP119
2.540
LEU120
3.330
THR144
4.746
SER145
3.274
ALA146
2.555
LYS147
3.435
PDB ID: 7A47      KRASG12C GDP form in complex with Cpd4
Method X-ray diffraction Resolution 2.16 Å Mutation Yes [13]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKCDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:32 or .A:57 or .A:59 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.886
CYS12
3.867
GLY13
2.873
VAL14
3.310
GLY15
3.024
LYS16
2.769
SER17
2.630
ALA18
2.789
PHE28
3.170
VAL29
3.750
ASP30
3.037
TYR32
4.995
Residue
Distance (Å)
ASP57
4.479
ALA59
3.295
ASN116
3.155
LYS117
3.111
CYS118
4.983
ASP119
2.796
LEU120
3.683
THR144
4.744
SER145
3.353
ALA146
2.774
LYS147
3.324
PDB ID: 7RP2      Crystal structure of Kas G12C in complex with 2H11 CLAMP
Method X-ray diffraction Resolution 2.20 Å Mutation Yes [5]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
LVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKSD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHKEK
169
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.762
CYS12
4.067
GLY13
2.966
VAL14
3.585
GLY15
2.904
LYS16
2.446
SER17
2.942
ALA18
2.827
PHE28
3.359
VAL29
4.356
ASP30
2.957
GLU31
3.166
Residue
Distance (Å)
TYR32
4.042
PRO34
4.803
ASP57
4.586
ASN116
3.078
LYS117
3.367
SER118
4.813
ASP119
2.796
LEU120
3.366
THR144
4.897
SER145
3.367
ALA146
2.650
LYS147
3.271
PDB ID: 6USX      Identification of the Clinical Development Candidate MRTX849, a Covalent KRASG12C Inhibitor for the Treatment of Cancer
Method X-ray diffraction Resolution 2.27 Å Mutation Yes [23]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

SLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLL
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.664
CYS12
3.092
GLY13
1.982
VAL14
2.948
GLY15
2.276
LYS16
1.926
SER17
2.034
ALA18
2.009
LEU19
4.637
PHE28
2.771
VAL29
1.978
ASP30
1.967
GLU31
1.367
Residue
Distance (Å)
TYR32
3.160
PRO34
4.187
ASP57
4.390
ASN116
2.352
LYS117
2.509
SER118
4.430
ASP119
1.830
LEU120
2.769
THR144
4.660
SER145
2.599
ALA146
2.197
LYS147
3.048
PDB ID: 7OO7      KRasG12C ligand complex
Method X-ray diffraction Resolution 1.48 Å Mutation Yes [9]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TSLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
LVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKSD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.807
CYS12
3.964
GLY13
2.973
VAL14
3.421
GLY15
3.113
LYS16
2.744
SER17
2.932
ALA18
2.741
LEU19
4.962
PHE28
3.135
VAL29
2.839
ASP30
2.803
Residue
Distance (Å)
GLU31
4.320
TYR32
3.789
ASP57
4.554
ASN116
3.094
LYS117
3.135
SER118
4.777
ASP119
2.848
LEU120
3.621
THR144
4.620
SER145
3.330
ALA146
2.842
LYS147
3.435
PDB ID: 5V9O      KRAS G12C inhibitor
Method X-ray diffraction Resolution 1.56 Å Mutation Yes [24]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKCDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.769
CYS12
3.839
GLY13
2.785
VAL14
3.318
GLY15
3.065
LYS16
2.807
SER17
2.934
ALA18
2.720
LEU19
4.868
PHE28
3.149
VAL29
3.011
ASP30
2.798
Residue
Distance (Å)
GLU31
4.883
TYR32
3.892
ASP57
4.597
ASN116
3.109
LYS117
3.117
CYS118
4.836
ASP119
2.670
LEU120
3.517
THR144
4.702
SER145
3.435
ALA146
2.845
LYS147
3.332
PDB ID: 7MDP      KRas G12C in complex with G-2897
Method X-ray diffraction Resolution 1.96 Å Mutation Yes [5]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKCDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.758
CYS12
4.305
GLY13
3.154
VAL14
3.615
GLY15
2.832
LYS16
1.300
SER17
3.082
ALA18
3.161
PHE28
3.890
VAL29
4.716
ASP30
2.644
GLU31
3.603
Residue
Distance (Å)
TYR32
4.243
PRO34
4.717
ASP57
4.650
ASN116
3.185
LYS117
3.423
ASP119
2.697
LEU120
3.653
THR144
4.827
SER145
3.329
ALA146
2.656
LYS147
3.038
PDB ID: 5V9L      KRAS G12C in bound to quinazoline based switch II pocket (SWIIP) binder
Method X-ray diffraction Resolution 1.98 Å Mutation Yes [24]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TCLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
CVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKCD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHKE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.834
CYS12
3.561
GLY13
2.469
VAL14
3.303
GLY15
2.993
LYS16
2.690
SER17
3.044
ALA18
2.834
PHE28
3.281
VAL29
3.564
ASP30
2.428
GLU31
4.418
Residue
Distance (Å)
TYR32
3.659
PRO34
4.903
ASP57
4.637
ASN116
3.169
LYS117
3.117
CYS118
4.907
ASP119
2.635
LEU120
3.477
THR144
4.844
SER145
3.491
ALA146
2.818
LYS147
3.457
PDB ID: 5V71      KRAS G12C in bound to quinazoline based switch II pocket (SWIIP) binder
Method X-ray diffraction Resolution 2.23 Å Mutation Yes [25]
PDB Sequence
GMTEYKLVVV
9
GACGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TCLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
CVFAINNTKS
89
FEDIHHYREQ
99

IKRVKDSEDV
109
PMVLVGNKCD
119
LPSRTVDTKQ
129
AQDLARSYGI
139
PFIETSAKTR
149

QGVDDAFYTL
159
VREIRKHKE
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:19 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.513
CYS12
4.040
GLY13
3.057
VAL14
3.313
GLY15
2.942
LYS16
2.612
SER17
2.745
ALA18
2.735
LEU19
4.949
PHE28
3.368
VAL29
2.889
ASP30
2.487
GLU31
4.389
Residue
Distance (Å)
TYR32
3.895
PRO34
4.816
ASP57
4.478
ASN116
3.102
LYS117
3.210
CYS118
4.943
ASP119
2.460
LEU120
3.502
THR144
4.855
SER145
3.629
ALA146
2.922
LYS147
3.569
PDB ID: 8AFC      CRYSTAL STRUCTURE OF KRAS-G12C IN COMPLEX WITH COMPOUND 12
Method X-ray diffraction Resolution 2.41 Å Mutation Yes [6]
PDB Sequence
MTEYKLVVVG
10
ACGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
QEEYSAMRDQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHHYREQI
100

KRVKDSEDVP
110
MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150

GVDDAFYTLV
160
REIRKHKEK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GDP or .GDP2 or .GDP3 or :3GDP;style chemicals stick;color identity;select .A:11 or .A:12 or .A:13 or .A:14 or .A:15 or .A:16 or .A:17 or .A:18 or .A:28 or .A:29 or .A:30 or .A:31 or .A:32 or .A:34 or .A:57 or .A:116 or .A:117 or .A:118 or .A:119 or .A:120 or .A:144 or .A:145 or .A:146 or .A:147; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ALA11
3.892
CYS12
4.029
GLY13
2.921
VAL14
3.368
GLY15
3.120
LYS16
2.778
SER17
2.985
ALA18
2.781
PHE28
3.477
VAL29
3.884
ASP30
2.776
GLU31
4.631
Residue
Distance (Å)
TYR32
3.926
PRO34
4.731
ASP57
4.475
ASN116
3.207
LYS117
3.174
SER118
4.901
ASP119
2.811
LEU120
3.426
THR144
4.660
SER145
3.449
ALA146
2.789
LYS147
3.457
References  Top
REF 1 Discovery of a Covalent Inhibitor of KRAS(G12C) (AMG 510) for the Treatment of Solid Tumors. J Med Chem. 2020 Jan 9;63(1):52-65.
REF 2 Modeling receptor flexibility in the structure-based design of KRAS(G12C) inhibitors. J Comput Aided Mol Des. 2022 Aug;36(8):591-604.
REF 3 The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Nov;575(7781):217-223.
REF 4 Discovery of N-(1-Acryloylazetidin-3-yl)-2-(1H-indol-1-yl)acetamides as Covalent Inhibitors of KRAS(G12C). ACS Med Chem Lett. 2019 Aug 20;10(9):1302-1308.
REF 5 Conformation-locking antibodies for the discovery and characterization of KRAS inhibitors. Nat Biotechnol. 2022 May;40(5):769-778.
REF 6 Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRAS(G12C) Inhibitor. J Med Chem. 2022 Nov 10;65(21):14614-14629.
REF 7 In situ selectivity profiling and crystal structure of SML-8-73-1, an active site inhibitor of oncogenic K-Ras G12C. Proc Natl Acad Sci U S A. 2014 Jun 17;111(24):8895-900.
REF 8 Computationally Empowered Workflow Identifies Novel Covalent Allosteric Binders for KRAS(G12C). ChemMedChem. 2020 May 19;15(10):827-832.
REF 9 Discovery of AZD4625, a Covalent Allosteric Inhibitor of the Mutant GTPase KRAS(G12C). J Med Chem. 2022 May 12;65(9):6940-6952.
REF 10 Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, and Selective Covalent Oral Inhibitor of KRASG12C. Cancer Discov. 2022 Jun 2;12(6):1500-1517.
REF 11 K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 2013 Nov 28;503(7477):548-51.
REF 12 The reactivity-driven biochemical mechanism of covalent KRAS(G12C) inhibitors. Nat Struct Mol Biol. 2018 Jun;25(6):454-462.
REF 13 KRAS G12C fragment screening renders new binding pockets. Small GTPases. 2022 Jan;13(1):225-238.
REF 14 Structure-Based Design and Pharmacokinetic Optimization of Covalent Allosteric Inhibitors of the Mutant GTPase KRAS(G12C). J Med Chem. 2020 May 14;63(9):4468-4483.
REF 15 Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor. Cell. 2018 Jan 25;172(3):578-589.e17.
REF 16 Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State. Cancer Discov. 2016 Mar;6(3):316-29.
REF 17 Co-crystal Structure of KRAS (G12C) covalently bound with Quinazoline based inhibitor JBI739
REF 18 Expanding the Scope of Electrophiles Capable of Targeting K-Ras Oncogenes. Biochemistry. 2017 Jun 27;56(25):3178-3183.
REF 19 Co-crystal Structure of KRAS (G12C) covalently bound with Quinazoline based inhibitor JBI484
REF 20 Discovery of Tetrahydropyridopyrimidines as Irreversible Covalent Inhibitors of KRAS-G12C with In Vivo Activity. ACS Med Chem Lett. 2018 Nov 7;9(12):1230-1234.
REF 21 Novel K-Ras G12C Switch-II Covalent Binders Destabilize Ras and Accelerate Nucleotide Exchange. J Chem Inf Model. 2018 Feb 26;58(2):464-471.
REF 22 Discovery and biological evaluation of 1-{2,7-diazaspiro[3.5]nonan-2-yl}prop-2-en-1-one derivatives as covalent inhibitors of KRAS G12C with favorable metabolic stability and anti-tumor activity. Bioorg Med Chem. 2022 Oct 1;71:116949.
REF 23 Identification of the Clinical Development Candidate MRTX849, a Covalent KRAS(G12C) Inhibitor for the Treatment of Cancer. J Med Chem. 2020 Jul 9;63(13):6679-6693.
REF 24 Potent and Selective Covalent Quinazoline Inhibitors of KRAS G12C. Cell Chem Biol. 2017 Aug 17;24(8):1005-1016.e3.
REF 25 KRAS G12C Drug Development: Discrimination between Switch II Pocket Configurations Using Hydrogen/Deuterium-Exchange Mass Spectrometry. Structure. 2017 Sep 5;25(9):1442-1448.e3.

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