› 6sis

X-ray diffraction
3.5Å resolution

Crystal structure of macrocyclic PROTAC 1 in complex with the second bromodomain of human Brd4 and pVHL:ElonginC:ElonginB

Released:
DOI: 10.2210/pdb6sis/pdb
PDB entry 6sis coloured by chain, front view.
PDB entry 6sis coloured by chain, side view.
PDB entry 6sis coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-Based Design of a Macrocyclic PROTAC.
Testa A, Hughes SJ, Lucas X, Wright JE, Ciulli A
Angew Chem Int Ed Engl 59 1727-1734 (2020)
PMID: 31746102

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-130120 (preferred)
Entry contents:
4 distinct polypeptide molecules
Macromolecules (4 distinct):
Bromodomain-containing protein 4 Chains: A, E
Molecule details ›
Chains: A, E
Length: 130 amino acids
Theoretical weight: 15.06 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: O60885 (Residues: 333-460; Coverage: 9%)
Gene names: BRD4, HUNK1
Sequence domains: Bromodomain
Elongin-B Chains: B, F
Molecule details ›
Chains: B, F
Length: 104 amino acids
Theoretical weight: 11.75 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
Elongin-C Chains: C, G
Molecule details ›
Chains: C, G
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
von Hippel-Lindau disease tumor suppressor Chains: D, H
Molecule details ›
Chains: D, H
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:

Ligands and Environments

1 bound ligand:
Ligand LFE 2 x LFE
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I04
Spacegroup: P32
Unit cell:
a: 99.459Å b: 99.459Å c: 148.426Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.221 0.22 0.247
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

32 review citations

Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy.
Li et al. (2020)
31 more

5 mentions without citation

Advancing targeted protein degradation for cancer therapy.
Dale et al. (2021)
4 more