› 6bvi

X-ray diffraction
1.75Å resolution

Ras:SOS:Ras in complex with a small molecule activator

Released:
DOI: 10.2210/pdb6bvi/pdb
PDB entry 6bvi coloured by chain, front view.
PDB entry 6bvi coloured by chain, side view.
PDB entry 6bvi coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of Aminopiperidine Indoles That Activate the Guanine Nucleotide Exchange Factor SOS1 and Modulate RAS Signaling.
Abbott JR, Hodges TR, Daniels RN, Patel PA, Kennedy JP, Howes JE, Akan DT, Burns MC, Sai J, Sobolik T, Beesetty Y, Lee T, Rossanese OW, Phan J, Waterson AG, Fesik SW
J Med Chem 61 6002-6017 (2018)
PMID: 29856609

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: A
Molecule details ›
Chain: A
Length: 167 amino acids
Theoretical weight: 18.86 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: B
Molecule details ›
Chain: B
Length: 482 amino acids
Theoretical weight: 56.59 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q07889 (Residues: 566-1046; Coverage: 36%)
Gene name: SOS1
Sequence domains:
Structure domains:
GTPase HRas, N-terminally processed Chain: C
Molecule details ›
Chain: C
Length: 167 amino acids
Theoretical weight: 18.93 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

Ligands and Environments

6 bound ligands:
Ligand GNP 1 x GNP
Ligand MG 1 x MG
Ligand EC4 1 x EC4
Ligand FMT 6 x FMT
Ligand GOL 2 x GOL
Ligand NA 1 x NA
1 modified residue:
Ligand CSO 1 x CSO

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 21-ID-F
Spacegroup: I422
Unit cell:
a: 184.323Å b: 184.323Å c: 179.091Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.157 0.156 0.169
Expression system: Escherichia coli

Quick links

Citations

3 review citations

Biology, pathology, and therapeutic targeting of RAS.
Rhett et al. (2020)
2 more

4 mentions without citation

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