› 6ut0

X-ray diffraction
1.94Å resolution

Identification of the Clinical Development Candidate MRTX849, a Covalent KRASG12C Inhibitor for the Treatment of Cancer

Released:
DOI: 10.2210/pdb6ut0/pdb
PDB entry 6ut0 coloured by chain, front view.
PDB entry 6ut0 coloured by chain, side view.
PDB entry 6ut0 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Identification of the Clinical Development Candidate
Fell JB, Fischer JP, Baer BR, Blake JF, Bouhana K, Briere DM, Brown KD, Burgess LE, Burns AC, Burkard MR, Chiang H, Chicarelli MJ, Cook AW, Gaudino JJ, Hallin J, Hanson L, Hartley DP, Hicken EJ, Hingorani GP, Hinklin RJ, Mejia MJ, Olson P, Otten JN, Rhodes SP, Rodriguez ME, Savechenkov P, Smith DJ, Sudhakar N, Sullivan FX, Tang TP, Vigers GP, Wollenberg L, Christensen JG, Marx MA
J Med Chem 63 6679-6693 (2020)
PMID: 32250617

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, C, D
Molecule details ›
Chains: A, B, C, D
Length: 170 amino acids
Theoretical weight: 19.35 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P01116 (Residues: 1-169; Coverage: 89%)
Gene names: KRAS, KRAS2, RASK2
Sequence domains: Ras family

Ligands and Environments

3 bound ligands:
Ligand GDP 4 x GDP
Ligand MG 4 x MG
Ligand M1X 4 x M1X
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E
Spacegroup: P21
Unit cell:
a: 74.918Å b: 61.8Å c: 76.05Å
α: 90° β: 111.37° γ: 90°
R-values:
R R work R free
0.177 0.175 0.222
Expression system: Escherichia coli

Quick links

Citations

57 review citations

KRAS mutation: from undruggable to druggable in cancer.
Huang et al. (2021)
56 more

21 mentions without citation

Covalent inhibitors: a rational approach to drug discovery.
Sutanto et al. (2020)
20 more