› 4nyj

X-ray diffraction
2.85Å resolution

Approach for Targeting Ras with Small Molecules that Activate SOS-Mediated Nucleotide Exchange

Released:
DOI: 10.2210/pdb4nyj/pdb
PDB entry 4nyj coloured by chain, front view.
PDB entry 4nyj coloured by chain, side view.
PDB entry 4nyj coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange.
Burns MC, Sun Q, Daniels RN, Camper D, Kennedy JP, Phan J, Olejniczak ET, Lee T, Waterson AG, Rossanese OW, Fesik SW
Proc Natl Acad Sci U S A 111 3401-6 (2014)
PMID: 24550516

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:
hetero trimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-133957 (preferred)
Entry contents:
3 distinct polypeptide molecules
Macromolecules (3 distinct):
GTPase HRas, N-terminally processed Chain: Q
Molecule details ›
Chain: Q
Length: 166 amino acids
Theoretical weight: 18.78 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P01112 (Residues: 1-166; Coverage: 88%)
Gene names: HRAS, HRAS1
Sequence domains: Ras family
Structure domains: P-loop containing nucleotide triphosphate hydrolases
GTPase HRas, N-terminally processed Chain: R
Molecule details ›
Chain: R
Length: 166 amino acids
Theoretical weight: 18.88 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P01112 (Residues: 1-166; Coverage: 88%)
Gene names: HRAS, HRAS1
Sequence domains: Ras family
Structure domains: P-loop containing nucleotide triphosphate hydrolases
Son of sevenless homolog 1 Chain: S
Molecule details ›
Chain: S
Length: 481 amino acids
Theoretical weight: 56.53 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q07889 (Residues: 566-1046; Coverage: 36%)
Gene name: SOS1
Sequence domains:
Structure domains:

Ligands and Environments

3 bound ligands:
Ligand MG 1 x MG
Ligand GNP 1 x GNP
Ligand 2PZ 1 x 2PZ
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 21-ID-F
Spacegroup: I422
Unit cell:
a: 185.338Å b: 185.338Å c: 179.535Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.157 0.156 0.187
Expression system: Escherichia coli

Quick links

Citations

31 review citations

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

9 mentions without citation

Structural Insights into the Regulation Mechanism of Small GTPases by GEFs.
Toma-Fukai et al. (2019)
8 more