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 T03046 Target Info
Target Name Mutated KRAS (mKRAS)
Synonyms c-Ki-ras (mutated); c-K-ras (mutated); RASK2 (mutated); Ki-Ras (mutated); KRAS2 (mutated); K-Ras 2 (mutated); GTPase KRas (mutated)
Target Type Clinical trial Target
Gene Name KRAS
UniProt ID
RASK_HUMAN
Ligand General Information  Top
Ligand Name Guanosine-5'-Triphosphate Ligand Info
Canonical SMILES C1=NC2=C(N1C3C(C(C(O3)COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O)O)N=C(NC2=O)N
InChI 1S/C10H16N5O14P3/c11-10-13-7-4(8(18)14-10)12-2-15(7)9-6(17)5(16)3(27-9)1-26-31(22,23)29-32(24,25)28-30(19,20)21/h2-3,5-6,9,16-17H,1H2,(H,22,23)(H,24,25)(H2,19,20,21)(H3,11,13,14,18)/t3-,5-,6-,9-/m1/s1
InChIKey XKMLYUALXHKNFT-UUOKFMHZSA-N
PubChem Compound ID 135398633
Drug Binding Sites of Target  Top
PDB ID: 5VPI      Crystal structure of human KRAS G12A mutant in complex with GTP
Method X-ray diffraction Resolution 1.62 Å Mutation Yes [1]
PDB Sequence
HMTEYKLVVV
9
GAAGVGKSAL
19
TIQLIQNHFV
29
DEYDPEDSYR
41
KQVVIDGETC
51

LLDILDTADQ
70
YMRTGEGFLC
80
VFAINNTKSF
90
EDIHHYREQI
100
KRVKDSEDVP
110

MVLVGNKSDL
120
PSRTVDTKQA
130
QDLARSYGIP
140
FIETSAKTRQ
150
GVDDAFYTLV
160

REIRKHKEK
Residue
Distance (Å)
GLY10
4.733
ALA11
3.801
ALA12
3.637
GLY13
3.009
VAL14
3.276
GLY15
3.047
LYS16
2.543
SER17
2.974
ALA18
2.833
PHE28
3.463
VAL29
2.896
ASP30
2.830
GLU31
4.081
TYR32
2.521
Residue
Distance (Å)
ASP33
4.345
PRO34
3.700
ASP57
4.629
THR58
3.993
ALA59
3.719
ASN116
3.107
LYS117
3.170
SER118
4.772
ASP119
2.756
LEU120
3.438
THR144
4.749
SER145
3.461
ALA146
2.893
LYS147
3.521
PDB ID: 5VQ2      Crystal structure of human WT-KRAS in complex with GTP
Method X-ray diffraction Resolution 1.96 Å Mutation Yes [1]
PDB Sequence
HMTEYKLVVV
9
GAGGVGKSAL
19
TIQLIQNHFV
29
DEYDEDSYRK
42
QVVIDGETCL
52

LDILDTDQYM
72
RTGEGFLCVF
82
AINNTKSFED
92
IHHYREQIKR
102
VKDSEDVPMV
112

LVGNKSDLPS
122
RTVDTKQAQD
132
LARSYGIPFI
142
ETSAKTRQGV
152
DDAFYTLVRE
162

IRKHKE
Residue
Distance (Å)
GLY10
4.846
ALA11
3.879
GLY12
3.400
GLY13
3.054
VAL14
3.290
GLY15
3.059
LYS16
2.672
SER17
2.941
ALA18
2.814
PHE28
3.343
VAL29
3.374
ASP30
3.091
GLU31
4.870
Residue
Distance (Å)
TYR32
4.884
ASP57
4.337
THR58
3.960
ASN116
3.175
LYS117
3.243
SER118
4.857
ASP119
2.735
LEU120
3.443
THR144
4.791
SER145
3.522
ALA146
2.871
LYS147
3.464
PDB ID: 6MNX      Structural basis of impaired hydrolysis in KRAS Q61H mutant
Method X-ray diffraction Resolution 2.20 Å Mutation Yes [2]
PDB Sequence
MTEYKLVVVG
10
AGGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
HEEAMRDQYM
72
RTGEGFLCVF
82
AINNTKSFED
92
IHHYREQIKR
102

VKDSEDVPMV
112
LVGNKCDLPS
122
RTVDTKQAQD
132
LARSYGIPFI
142
ETSAKTRQGV
152

DDAFYTLVRE
162
IRKHKEK
Residue
Distance (Å)
GLY10
4.250
ALA11
3.757
GLY12
2.014
GLY13
2.172
VAL14
2.912
GLY15
2.086
LYS16
1.897
SER17
1.985
ALA18
2.049
LEU19
4.440
PHE28
2.528
VAL29
2.233
ASP30
2.298
GLU31
3.305
TYR32
1.744
ASP33
3.549
Residue
Distance (Å)
PRO34
2.728
THR35
2.097
ASP57
3.668
THR58
3.437
ALA59
3.317
GLY60
1.873
HIS61
4.005
ASN116
2.476
LYS117
2.521
CYS118
4.693
ASP119
1.732
LEU120
2.505
THR144
4.839
SER145
2.714
ALA146
2.376
LYS147
2.745
References  Top
REF 1 Structural insight into the rearrangement of the switch I region in GTP-bound G12A K-Ras. Acta Crystallogr D Struct Biol. 2017 Dec 1;73(Pt 12):970-984.
REF 2 KRAS(Q61H) Preferentially Signals through MAPK in a RAF Dimer-Dependent Manner in Non-Small Cell Lung Cancer. Cancer Res. 2020 Sep 1;80(17):3719-3731.

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