› 5oco

X-ray diffraction
1.66Å resolution

Discovery of small molecules binding to KRAS via high affinity antibody fragment competition method.

Released:
DOI: 10.2210/pdb5oco/pdb
PDB entry 5oco coloured by chain, front view.
PDB entry 5oco coloured by chain, side view.
PDB entry 5oco coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment.
Quevedo CE, Cruz-Migoni A, Bery N, Miller A, Tanaka T, Petch D, Bataille CJR, Lee LYW, Fallon PS, Tulmin H, Ehebauer MT, Fernandez-Fuentes N, Russell AJ, Carr SB, Phillips SEV, Rabbitts TH
Nat Commun 9 3169 (2018)
PMID: 30093669

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:
homo hexamer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-134033 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
GTPase KRas, N-terminally processed Chains: A, B, C, D, E, F
Molecule details ›
Chains: A, B, C, D, E, F
Length: 187 amino acids
Theoretical weight: 21.5 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
Structure domains: P-loop containing nucleotide triphosphate hydrolases

Ligands and Environments

5 bound ligands:
Ligand GNP 6 x GNP
Ligand 9RK 5 x 9RK
Ligand PEG 1 x PEG
Ligand MG 6 x MG
Ligand CIT 3 x CIT
1 modified residue:
Ligand CSO 6 x CSO

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I02
Spacegroup: P212121
Unit cell:
a: 63.6Å b: 118.76Å c: 156.9Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.18 0.179 0.205
Expression system: Escherichia coli

Quick links

Citations

23 review citations

RAS-targeted therapies: is the undruggable drugged?
Moore et al. (2020)
22 more

5 mentions without citation

RAS Nanoclusters: Dynamic Signaling Platforms Amenable to Therapeutic Intervention.
Van et al. (2021)
4 more