› 4dst

X-ray diffraction
2.3Å resolution

Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity

Released:
DOI: 10.2210/pdb4dst/pdb
PDB entry 4dst coloured by chain, front view.
PDB entry 4dst coloured by chain, side view.
PDB entry 4dst coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity.
Maurer T, Garrenton LS, Oh A, Pitts K, Anderson DJ, Skelton NJ, Fauber BP, Pan B, Malek S, Stokoe D, Ludlam MJ, Bowman KK, Wu J, Giannetti AM, Starovasnik MA, Mellman I, Jackson PK, Rudolph J, Wang W, Fang G
Proc Natl Acad Sci U S A 109 5299-304 (2012)
PMID: 22431598

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)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
GTPase KRas Chain: A
Molecule details ›
Chain: A
Length: 189 amino acids
Theoretical weight: 21.53 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P01116 (Residues: 2-189; Coverage: 99%)
Gene names: KRAS, KRAS2, RASK2
Sequence domains: Ras family
Structure domains: P-loop containing nucleotide triphosphate hydrolases

Ligands and Environments

7 bound ligands:
Ligand 9LI 1 x 9LI
Ligand GCP 1 x GCP
Ligand MG 2 x MG
Ligand GOL 1 x GOL
Ligand EDO 1 x EDO
Ligand DMS 1 x DMS
Ligand ACT 1 x ACT
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: R3
Unit cell:
a: 78.923Å b: 78.923Å c: 78.631Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.162 0.159 0.209
Expression system: Escherichia coli

Quick links

Citations

118 review citations

RAS Proteins and Their Regulators in Human Disease.
Simanshu et al. (2017)
117 more

28 mentions without citation

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