› 7z77

X-ray diffraction
1.97Å resolution

Crystal structure of compound 6 in complex with the bromodomain of human SMARCA2 and pVHL:ElonginC:ElonginB

Released:
DOI: 10.2210/pdb7z77/pdb
PDB entry 7z77 coloured by chain, front view.
PDB entry 7z77 coloured by chain, side view.
PDB entry 7z77 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo.
Kofink C, Trainor N, Mair B, Wöhrle S, Wurm M, Mischerikow N, Roy MJ, Bader G, Greb P, Garavel G, Diers E, McLennan R, Whitworth C, Vetma V, Rumpel K, Scharnweber M, Fuchs JE, Gerstberger T, Cui Y, Gremel G, Chetta P, Hopf S, Budano N, Rinnenthal J, Gmaschitz G, Mayer M, Koegl M, Ciulli A, Weinstabl H, Farnaby W
Nat Commun 13 5969 (2022)
PMID: 36216795

Function and Biology Details

Biochemical function:
  • not assigned
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero tetramer (preferred)
PDBe Complex ID:
PDB-CPX-154076 (preferred)
Entry contents:
4 distinct polypeptide molecules
Macromolecules (4 distinct):
Elongin-B Chain: A
Molecule details ›
Chain: A
Length: 104 amino acids
Theoretical weight: 11.75 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q15370 (Residues: 1-104; Coverage: 88%)
Gene names: ELOB, TCEB2
Sequence domains: Ubiquitin family
Elongin-C Chain: B
Molecule details ›
Chain: B
Length: 97 amino acids
Theoretical weight: 10.97 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: 162 amino acids
Theoretical weight: 18.7 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P40337 (Residues: 54-213; Coverage: 75%)
Gene name: VHL
Sequence domains:
Probable global transcription activator SNF2L2 Chain: D
Molecule details ›
Chain: D
Length: 123 amino acids
Theoretical weight: 14.38 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P51531 (Residues: 1373-1511; Coverage: 8%)
Gene names: BAF190B, BRM, SMARCA2, SNF2A, SNF2L2
Sequence domains: Bromodomain

Ligands and Environments

1 bound ligand:
Ligand IFF 1 x IFF
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P21
Unit cell:
a: 48.903Å b: 63.707Å c: 91.956Å
α: 90° β: 101.32° γ: 90°
R-values:
R R work R free
0.215 0.213 0.251
Expression system: Escherichia coli

Quick links

Citations

9 review citations

Expanding Chemical Probe Space: Quality Criteria for Covalent and Degrader Probes.
Hartung et al. (2023)
8 more

1 mention without citation

A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo.
Kofink et al. (2022)