› 7khh

X-ray diffraction
2.28Å resolution

Ternary complex of VHL/BRD4-BD1/Compound9 (4-(3,5-difluoropyridin-2-yl)-N-(11-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-11-oxoundecyl)-10-methyl-7-((methylsulfonyl)methyl)-11-oxo-3,4,10,11-tetrahydro-1H-1,4,10-triazadibenzo[cd,f]azulene-6-carboxamide)

Released:
DOI: 10.2210/pdb7khh/pdb
PDB entry 7khh coloured by chain, front view.
PDB entry 7khh coloured by chain, side view.
PDB entry 7khh coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 2: Improvement of In Vitro Antiproliferation Activity and In Vivo Antitumor Efficacy.
Dragovich PS, Pillow TH, Blake RA, Sadowsky JD, Adaligil E, Adhikari P, Chen J, Corr N, Dela Cruz-Chuh J, Del Rosario G, Fullerton A, Hartman SJ, Jiang F, Kaufman S, Kleinheinz T, Kozak KR, Liu L, Lu Y, Mulvihill MM, Murray JM, O'Donohue A, Rowntree RK, Sawyer WS, Staben LR, Wai J, Wang J, Wei B, Wei W, Xu Z, Yao H, Yu SF, Zhang D, Zhang H, Zhang S, Zhao Y, Zhou H, Zhu X
J Med Chem 64 2576-2607 (2021)
PMID: 33596073

Function and Biology Details

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

Structure analysis Details

Assembly composition:
hetero tetramer (preferred)
PDBe Complex ID:
PDB-CPX-130120 (preferred)
Entry contents:
4 distinct polypeptide molecules
Macromolecules (4 distinct):
Elongin-B Chain: A
Molecule details ›
Chain: A
Length: 118 amino acids
Theoretical weight: 13.16 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q15370 (Residues: 1-118; Coverage: 100%)
Gene names: ELOB, TCEB2
Sequence domains: Ubiquitin family
Elongin-C Chain: B
Molecule details ›
Chain: B
Length: 96 amino acids
Theoretical weight: 10.84 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q15369 (Residues: 17-112; Coverage: 86%)
Gene names: ELOC, TCEB1
Sequence domains: Skp1 family, tetramerisation domain
von Hippel-Lindau disease tumor suppressor Chain: C
Molecule details ›
Chain: C
Length: 175 amino acids
Theoretical weight: 20.38 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P40337 (Residues: 55-213; Coverage: 75%)
Gene name: VHL
Sequence domains:
Bromodomain-containing protein 4 Chain: D
Molecule details ›
Chain: D
Length: 149 amino acids
Theoretical weight: 17.63 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: O60885 (Residues: 44-168; Coverage: 9%)
Gene names: BRD4, HUNK1
Sequence domains: Bromodomain

Ligands and Environments

1 bound ligand:
Ligand WEP 1 x WEP
1 modified residue:
Ligand CSX 1 x CSX

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 21-ID-D
Spacegroup: P3121
Unit cell:
a: 78.979Å b: 78.979Å c: 195.399Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.18 0.178 0.229
Expression system: Escherichia coli

Quick links

Citations

24 review citations

PROTAC targeted protein degraders: the past is prologue.
Békés et al. (2022)
23 more

4 mentions without citation

Discovery of small molecule ligands for the von Hippel-Lindau (VHL) E3 ligase and their use as inhibitors and PROTAC degraders.
Diehl et al. (2022)
3 more