› 5nw1

X-ray diffraction
2.1Å resolution

pVHL:EloB:EloC in complex with (2S,4R)-1-((S)-2-(cyclobutanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 18)

Released:
DOI: 10.2210/pdb5nw1/pdb
PDB entry 5nw1 coloured by chain, front view.
PDB entry 5nw1 coloured by chain, side view.
PDB entry 5nw1 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Group-Based Optimization of Potent and Cell-Active Inhibitors of the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase: Structure-Activity Relationships Leading to the Chemical Probe (2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (VH298).
Soares P, Gadd MS, Frost J, Galdeano C, Ellis L, Epemolu O, Rocha S, Read KD, Ciulli A
OpenAccess logo J Med Chem 61 599-618 (2018)
PMID: 28853884

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 9BH 4 x 9BH
1 modified residue:
Ligand CAS 12 x CAS

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I04-1
Spacegroup: P4122
Unit cell:
a: 94.591Å b: 94.591Å c: 368.091Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.198 0.196 0.238
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

24 review citations

PROteolysis TArgeting Chimeras (PROTACs) - Past, present and future.
Pettersson et al. (2019)
23 more

1 mention without citation

Group-Based Optimization of Potent and Cell-Active Inhibitors of the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase: Structure-Activity Relationships Leading to the Chemical Probe (2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (VH298).
Soares et al. (2018)