› 5ij8

X-ray diffraction
2.99Å resolution

Structure of the primary oncogenic mutant Y641N Hs/AcPRC2 in complex with a pyridone inhibitor

Released:
DOI: 10.2210/pdb5ij8/pdb
PDB entry 5ij8 coloured by chain, front view.
PDB entry 5ij8 coloured by chain, side view.
PDB entry 5ij8 coloured by chain, top view.
Source organisms:
Primary publication:
Polycomb repressive complex 2 structure with inhibitor reveals a mechanism of activation and drug resistance.
Brooun A, Gajiwala KS, Deng YL, Liu W, Bolaños B, Bingham P, He YA, Diehl W, Grable N, Kung PP, Sutton S, Maegley KA, Yu X, Stewart AE
Nat Commun 7 11384 (2016)
PMID: 27122193

Function and Biology Details

Reaction catalysed: 
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine(27) = S-adenosyl-L-homocysteine + a [histone H3]-N(6)-methyl-L-lysine(27)
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
hetero trimer (preferred)
PDBe Complex ID:
PDB-CPX-124199 (preferred)
Entry contents:
3 distinct polypeptide molecules
Macromolecules (3 distinct):
Histone-lysine N-methyltransferase EZH2 Chains: A, B
Molecule details ›
Chains: A, B
Length: 643 amino acids
Theoretical weight: 72.89 KDa
Source organisms: Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: Q15910 (Residues: 1-12, 511-531, 533-746; Coverage: 33%)
  • Canonical: G1KPH4 (Residues: 28-514; Coverage: 49%)
Gene names: EZH2, KMT6
Sequence domains:
Polycomb protein EED Chains: E, F
Molecule details ›
Chains: E, F
Length: 362 amino acids
Theoretical weight: 41.78 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: O75530 (Residues: 80-441; Coverage: 82%)
Gene name: EED
Sequence domains: WD domain, G-beta repeat
Structure domains: YVTN repeat-like/Quinoprotein amine dehydrogenase
Polycomb protein SUZ12 Chains: S, T
Molecule details ›
Chains: S, T
Length: 191 amino acids
Theoretical weight: 22.27 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: Q15022 (Residues: 545-725; Coverage: 25%)
Gene names: CHET9, JJAZ1, KIAA0160, SUZ12
Sequence domains: VEFS-Box of polycomb protein

Ligands and Environments

2 bound ligands:
Ligand 6BN 2 x 6BN
Ligand ZN 14 x ZN
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P21
Unit cell:
a: 71.331Å b: 115.133Å c: 153.939Å
α: 90° β: 103.35° γ: 90°
R-values:
R R work R free
0.191 0.188 0.24
Expression system: Spodoptera frugiperda

Quick links

Citations

33 review citations

PRC2 is high maintenance.
Yu et al. (2019)
32 more

5 mentions without citation

Inhibitors of Protein Methyltransferases and Demethylases.
Kaniskan et al. (2018)
4 more