› 4epw

X-ray diffraction
1.7Å resolution

Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-mediated Activation

Released:
DOI: 10.2210/pdb4epw/pdb
PDB entry 4epw coloured by chain, front view.
PDB entry 4epw coloured by chain, side view.
PDB entry 4epw coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of small molecules that bind to K-Ras and inhibit Sos-mediated activation.
Sun Q, Burke JP, Phan J, Burns MC, Olejniczak ET, Waterson AG, Lee T, Rossanese OW, Fesik SW
Angew Chem Int Ed Engl 51 6140-3 (2012)
PMID: 22566140

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 Chain: A
Molecule details ›
Chain: A
Length: 170 amino acids
Theoretical weight: 19.31 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P01116 (Residues: 1-169; Coverage: 89%)
  • Best match: P01116-2 (Residues: 1-169)
Gene names: KRAS, KRAS2, RASK2
Sequence domains: Ras family
Structure domains: P-loop containing nucleotide triphosphate hydrolases

Ligands and Environments

3 bound ligands:
Ligand GDP 1 x GDP
Ligand MG 1 x MG
Ligand 0QV 1 x 0QV
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: BRUKER AXS MICROSTAR
Spacegroup: P212121
Unit cell:
a: 39.219Å b: 41.924Å c: 91.448Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.188 0.186 0.24
Expression system: Escherichia coli

Quick links

Citations

88 review citations

Drugging the undruggable RAS: Mission possible?
Cox et al. (2014)
87 more

11 mentions without citation

Structure-based inhibitor design of mutant RAS proteins-a paradigm shift.
Nyíri et al. (2020)
10 more