› 6p8w

X-ray diffraction
2.1Å resolution

Crystal structure of human KRAS G12C covalently bound to an acryloylazetidine acetamide inhibitor.

Released:
DOI: 10.2210/pdb6p8w/pdb
Model geometry
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PDB entry 6p8w coloured by chain, front view.
PDB entry 6p8w coloured by chain, side view.
PDB entry 6p8w coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of N-(1-Acryloylazetidin-3-yl)-2-(1H-indol-1-yl)acetamides as Covalent Inhibitors of KRASG12C.
Shin Y, Jeong JW, Wurz RP, Achanta P, Arvedson T, Bartberger MD, Campuzano IDG, Fucini R, Hansen SK, Ingersoll J, Iwig JS, Lipford JR, Ma V, Kopecky DJ, McCarter J, San Miguel T, Mohr C, Sabet S, Saiki AY, Sawayama A, Sethofer S, Tegley CM, Volak LP, Yang K, Lanman BA, Erlanson DA, Cee VJ
ACS Med Chem Lett 10 1302-1308 (2019)
PMID: 31531201

Function and Biology Details

Reaction catalysed: 
GTP + H(2)O = GDP + phosphate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-133991 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
GTPase KRas, N-terminally processed Chains: A, B
Molecule details ›
Chains: A, B
Length: 183 amino acids
Theoretical weight: 21.04 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P01116 (Residues: 1-169; Coverage: 89%)
  • Best match: P01116-2 (Residues: 1-169)
Gene names: KRAS, KRAS2, RASK2
Sequence domains: Ras family

Ligands and Environments

3 bound ligands:
Ligand CA 4 x CA
Ligand GDP 2 x GDP
Ligand O67 2 x O67
No modified residues

Experiments and Validation Details

wwPDB Validation report is not available for this entry.
X-ray source: RIGAKU FR-E SUPERBRIGHT
Spacegroup: P1
Unit cell:
a: 32.848Å b: 39.084Å c: 61.847Å
α: 78.3° β: 81.43° γ: 77.3°
R-values:
R R work R free
0.232 0.23 0.277
Expression system: Escherichia coli BL21(DE3)

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Citations

14 review citations

Advances in covalent drug discovery.
Boike et al. (2022)
13 more

2 mentions without citation

Discovery of N-(1-Acryloylazetidin-3-yl)-2-(1H-indol-1-yl)acetamides as Covalent Inhibitors of KRASG12C.
Shin et al. (2019)
1 more

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