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 T48598 Target Info
Target Name GTPase KRas (KRAS)
Synonyms c-Ki-ras; c-K-ras; RASK2; Ki-Ras; KRAS2; K-Ras 2
Target Type Clinical trial Target
Gene Name KRAS
Biochemical Class Small GTPase
UniProt ID
RASK_HUMAN
Ligand General Information  Top
Ligand Name 1-[4-[6-Chloro-7-(2-fluorophenyl)quinazolin-4-yl]piperazin-1-yl]propan-1-one Ligand Info
Canonical SMILES CCC(=O)N1CCN(CC1)C2=NC=NC3=CC(=C(C=C32)Cl)C4=CC=CC=C4F
InChI 1S/C21H20ClFN4O/c1-2-20(28)26-7-9-27(10-8-26)21-16-11-17(22)15(12-19(16)24-13-25-21)14-5-3-4-6-18(14)23/h3-6,11-13H,2,7-10H2,1H3
InChIKey JPFKOCMCIFOGHK-UHFFFAOYSA-N
PubChem Compound ID 137348773
Drug Binding Sites of Target  Top
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 [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
REIRKHKE
Residue
Distance (Å)
VAL9
3.525
GLY10
3.165
ALA11
4.063
CYS12
1.671
GLY13
4.742
LYS16
2.802
PRO34
3.200
THR58
3.829
ALA59
3.268
GLY60
3.365
GLN61
3.964
GLU62
3.573
Residue
Distance (Å)
GLU63
4.739
ARG68
3.418
ASP69
3.939
MET72
3.589
PHE78
4.962
HIS95
3.032
TYR96
3.311
GLN99
3.477
ILE100
3.750
ARG102
3.956
VAL103
3.870
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 [2]
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
Residue
Distance (Å)
VAL9
3.238
GLY10
3.442
ALA11
4.439
CYS12
1.828
GLY13
4.456
LYS16
2.915
PRO34
3.532
THR58
3.614
ALA59
3.605
Residue
Distance (Å)
GLY60
3.669
ARG68
3.670
MET72
3.712
PHE78
4.496
HIS95
2.972
TYR96
3.040
GLN99
3.807
ILE100
3.865
VAL103
3.460
References  Top
REF 1 The reactivity-driven biochemical mechanism of covalent KRAS(G12C) inhibitors. Nat Struct Mol Biol. 2018 Jun;25(6):454-462.
REF 2 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.

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