› 4w9j

X-ray diffraction
2.2Å resolution

pVHL:EloB:EloC in complex with (2S,4R)-1-((S)-2-((S)-2-acetamido-4-methylpentanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 13)

Released:
DOI: 10.2210/pdb4w9j/pdb
PDB entry 4w9j coloured by chain, front view.
PDB entry 4w9j coloured by chain, side view.
PDB entry 4w9j coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-guided design and optimization of small molecules targeting the protein-protein interaction between the von Hippel-Lindau (VHL) E3 ubiquitin ligase and the hypoxia inducible factor (HIF) alpha subunit with in vitro nanomolar affinities.
Galdeano C, Gadd MS, Soares P, Scaffidi S, Van Molle I, Birced I, Hewitt S, Dias DM, Ciulli A
J Med Chem 57 8657-63 (2014)
PMID: 25166285

Function and Biology Details

Biochemical function:
  • not assigned
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: 104 amino acids
Theoretical weight: 11.96 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q15370 (Residues: 1-104; Coverage: 88%)
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: 17-112; Coverage: 86%)
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: 18.81 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

1 bound ligand:
Ligand 3JH 4 x 3JH
1 modified residue:
Ligand CAS 12 x CAS

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE BM14
Spacegroup: P4122
Unit cell:
a: 93.708Å b: 93.708Å c: 360.836Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.219 0.217 0.265
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

55 review citations

Induced protein degradation: an emerging drug discovery paradigm.
Lai et al. (2017)
54 more

2 mentions without citation

Structure-guided design and optimization of small molecules targeting the protein-protein interaction between the von Hippel-Lindau (VHL) E3 ubiquitin ligase and the hypoxia inducible factor (HIF) alpha subunit with in vitro nanomolar affinities.
Galdeano et al. (2014)
1 more