Target Binding Site Detail

Content Navigation (  All   None )                                      
Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T35486 Target Info
Target Name GTPase NRas (NRAS)
Synonyms Transforming protein N-Ras; HRAS1
Target Type Clinical trial Target
Gene Name NRAS
Biochemical Class Small GTPase
UniProt ID
RASN_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: 3CON      Crystal structure of the human NRAS GTPase bound with GDP
Method X-ray diffraction Resolution 1.65 Å Mutation No [1]
PDB Sequence
MTEYKLVVVG
10
AGGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
MRTGEGFLCV
81
FAINNSKSFA
91
DINLYREQIK
101
RVKDSDDVPM
111

VLVGNKCDLP
121
TRTVDTKQAH
131
ELAKSYGIPF
141
IETSAKTRQG
151
VEDAFYTLVR
161

EIRQYR
Residue
Distance (Å)
ALA11
3.836
GLY12
3.865
GLY13
2.847
VAL14
3.256
GLY15
3.044
LYS16
2.815
SER17
3.035
ALA18
2.774
PHE28
3.222
VAL29
2.671
ASP30
2.787
GLU31
3.952
Residue
Distance (Å)
TYR32
3.585
PRO34
4.798
ASP57
4.661
ASN116
3.034
LYS117
3.072
CYS118
4.776
ASP119
2.680
LEU120
3.552
THR144
4.591
SER145
3.337
ALA146
2.866
LYS147
3.425
PDB ID: 6WGH      Crystal structure of GDP-bound NRAS with ten residues long internal tandem duplication in the switch II region
Method X-ray diffraction Resolution 1.65 Å Mutation No [2]
PDB Sequence
GMTEYKLVVV
9
GAGGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TCLLDILDTA
59
GSAMRDQYMR
83
TGEGFLCVFA
93
INNSKSFADI
103
NLYREQIKRV
113

KDSDDVPMVL
123
VGNKCDLPTR
133
TVDTKQAHEL
143
AKSYGIPFIE
153
TSAKTRQGVE
163

DAFYTLVREI
173
RQYRMK
Residue
Distance (Å)
ALA11
3.919
GLY12
3.919
GLY13
2.864
VAL14
3.381
GLY15
3.081
LYS16
2.633
SER17
2.932
ALA18
2.672
LEU19
4.927
PHE28
3.139
VAL29
3.012
ASP30
2.850
Residue
Distance (Å)
GLU31
4.955
TYR32
3.809
ASP57
4.615
ASN126
3.054
LYS127
3.071
CYS128
4.847
ASP129
2.748
LEU130
3.325
THR154
4.739
SER155
3.454
ALA156
2.834
LYS157
3.426
PDB ID: 6ZIO      CRYSTAL STRUCTURE OF NRAS (C118S) IN COMPLEX WITH GDP
Method X-ray diffraction Resolution 1.55 Å Mutation Yes [3]
PDB Sequence
GMTEYKLVVV
9
GAGGVGKSAL
19
TIQLIQNHFV
29
DEYDPTIEDS
39
YRKQVVIDGE
49

TCLLDILDTA
59
GQEEYSAMRD
69
QYMRTGEGFL
79
CVFAINNSKS
89
FADINLYREQ
99

IKRVKDSDDV
109
PMVLVGNKSD
119
LPTRTVDTKQ
129
AHELAKSYGI
139
PFIETSAKTR
149

QGVEDAFYTL
159
VREIRQYRMK
169
K
Residue
Distance (Å)
ALA11
3.727
GLY12
3.859
GLY13
2.850
VAL14
3.254
GLY15
3.070
LYS16
2.775
SER17
3.046
ALA18
2.897
PHE28
3.264
VAL29
2.727
ASP30
2.698
GLU31
4.288
Residue
Distance (Å)
TYR32
3.724
PRO34
4.736
ASP57
4.611
ASN116
3.129
LYS117
3.129
SER118
4.910
ASP119
2.741
LEU120
3.486
THR144
4.728
SER145
3.345
ALA146
2.773
LYS147
3.409
PDB ID: 6ZIR      CRYSTAL STRUCTURE OF NRAS (C118S) IN COMPLEX WITH GDP AND COMPOUND 18
Method X-ray diffraction Resolution 1.90 Å Mutation Yes [3]
PDB Sequence
MTEYKLVVVG
10
AGGVGKSALT
20
IQLIQNHFVD
30
EYDPTIEDSY
40
RKQVVIDGET
50

CLLDILDTAG
60
MRDQYMRTGE
76
GFLCVFAINN
86
SKSFADINLY
96
REQIKRVKDS
106

DDVPMVLVGN
116
KSDLPTRTVD
126
TKQAHELAKS
136
YGIPFIETSA
146
KTRQGVEDAF
156

YTLVREIRQY
166
RMK
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
3.794
GLY12
3.760
GLY13
2.798
VAL14
3.326
GLY15
3.144
LYS16
2.753
SER17
2.921
ALA18
2.783
PHE28
3.254
VAL29
3.268
ASP30
2.840
GLU31
4.536
Residue
Distance (Å)
TYR32
3.822
PRO34
4.700
ASP57
4.446
ASN116
3.158
LYS117
3.108
SER118
4.857
ASP119
2.766
LEU120
3.486
THR144
4.559
SER145
3.378
ALA146
2.816
LYS147
3.521
References  Top
REF 1 Crystal structure of the human NRAS GTPase bound with GDP.
REF 2 RAS internal tandem duplication disrupts GTPase-activating protein (GAP) binding to activate oncogenic signaling. J Biol Chem. 2020 Jul 10;295(28):9335-9348.
REF 3 Drugging all RAS isoforms with one pocket. Future Med Chem. 2020 Nov;12(21):1911-1923.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.