› 4ekg

X-ray diffraction
2.8Å resolution

Crystal Structure of DOT1L in Complex with EPZ003696

Released:
DOI: 10.2210/pdb4ekg/pdb
PDB entry 4ekg coloured by chain, front view.
PDB entry 4ekg coloured by chain, side view.
PDB entry 4ekg coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Conformational adaptation drives potent, selective and durable inhibition of the human protein methyltransferase DOT1L.
Basavapathruni A, Jin L, Daigle SR, Majer CR, Therkelsen CA, Wigle TJ, Kuntz KW, Chesworth R, Pollock RM, Scott MP, Moyer MP, Richon VM, Copeland RA, Olhava EJ
Chem Biol Drug Des 80 971-80 (2012)
PMID: 22978415

Function and Biology Details

Reaction catalysed: 
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine(79) = S-adenosyl-L-homocysteine + a [histone H3]-N(6)-methyl-L-lysine(79)
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-186244 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Histone-lysine N-methyltransferase, H3 lysine-79 specific Chain: A
Molecule details ›
Chain: A
Length: 425 amino acids
Theoretical weight: 48.57 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q8TEK3 (Residues: 1-416; Coverage: 27%)
Gene names: DOT1L, KIAA1814, KMT4
Sequence domains: Histone methylation protein DOT1
Structure domains:

Ligands and Environments

1 bound ligand:
Ligand 0QJ 1 x 0QJ
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRF BEAMLINE BL17U
Spacegroup: P65
Unit cell:
a: 157.6Å b: 157.6Å c: 49.15Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.213 0.21 0.261
Expression system: Escherichia coli

Quick links

Citations

43 review citations

The drug-target residence time model: a 10-year retrospective.
Copeland RA. (2016)
42 more

2 mentions without citation

Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L.
Worden et al. (2019)
1 more