› 4b95

X-ray diffraction
2.8Å resolution

pVHL-EloB-EloB-EloC complex_(2S,4R)-1-(2-chlorophenyl)carbonyl-N-[(4-chlorophenyl)methyl]-4-oxidanyl-pyrrolidine-2-carboxamide bound

Released:
DOI: 10.2210/pdb4b95/pdb
PDB entry 4b95 coloured by chain, front view.
PDB entry 4b95 coloured by chain, side view.
PDB entry 4b95 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Small-molecule inhibitors of the interaction between the E3 ligase VHL and HIF1α.
Buckley DL, Gustafson JL, Van Molle I, Roth AG, Tae HS, Gareiss PC, Jorgensen WL, Ciulli A, Crews CM
Angew Chem Int Ed Engl 51 11463-7 (2012)
PMID: 23065727

Function and Biology Details

Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero trimer (preferred)
PDBe Complex ID:
PDB-CPX-154086 (preferred)
Entry contents:
3 distinct polypeptide molecules
Macromolecules (3 distinct):
Elongin-B Chains: A, D, G, J
Molecule details ›
Chains: A, D, G, J
Length: 118 amino acids
Theoretical weight: 13.15 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q15370 (Residues: 1-118; Coverage: 100%)
Gene names: ELOB, TCEB2
Sequence domains: Ubiquitin family
Structure domains: Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 1
Elongin-C Chains: B, E, H, K
Molecule details ›
Chains: B, E, H, K
Length: 97 amino acids
Theoretical weight: 10.97 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q15369 (Residues: 18-112; Coverage: 85%)
Gene names: ELOC, TCEB1
Sequence domains: Skp1 family, tetramerisation domain
Structure domains: Potassium Channel Kv1.1; Chain A
von Hippel-Lindau disease tumor suppressor Chains: C, F, I, L
Molecule details ›
Chains: C, F, I, L
Length: 162 amino acids
Theoretical weight: 18.7 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P40337 (Residues: 54-213; Coverage: 75%)
Gene name: VHL
Sequence domains:
Structure domains:

Ligands and Environments

2 bound ligands:
Ligand ACT 1 x ACT
Ligand UCK 4 x UCK
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SOLEIL BEAMLINE PROXIMA 1
Spacegroup: P4122
Unit cell:
a: 93.04Å b: 93.04Å c: 362.43Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.187 0.185 0.236
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

68 review citations

Small-molecule inhibitors of protein-protein interactions: progressing toward the reality.
Arkin et al. (2014)
67 more

2 mentions without citation

Discovery of novel inhibitors disrupting HIF-1α/von Hippel-Lindau interaction through shape-based screening and cascade docking.
Xue et al. (2016)
1 more