› 5dtm

X-ray diffraction
2.2Å resolution

Crystal structure of Dot1L in complex with inhibitor CPD1 [4-(2,6-dichlorobenzoyl)-N-methyl-1H-pyrrole-2-carboxamide]

Released:
DOI: 10.2210/pdb5dtm/pdb
PDB entry 5dtm coloured by chain, front view.
PDB entry 5dtm coloured by chain, side view.
PDB entry 5dtm coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Optimization of a Fragment-Based Screening Hit toward Potent DOT1L Inhibitors Interacting in an Induced Binding Pocket.
Scheufler C, Möbitz H, Gaul C, Ragot C, Be C, Fernández C, Beyer KS, Tiedt R, Stauffer F
ACS Med Chem Lett 7 730-4 (2016)
PMID: 27563394

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 Chains: A, B
Molecule details ›
Chains: A, B
Length: 334 amino acids
Theoretical weight: 38.46 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q8TEK3 (Residues: 2-332; Coverage: 22%)
Gene names: DOT1L, KIAA1814, KMT4
Sequence domains: Histone methylation protein DOT1
Structure domains:

Ligands and Environments

1 bound ligand:
Ligand 5F4 2 x 5F4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P63
Unit cell:
a: 158.559Å b: 158.559Å c: 73.396Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.176 0.174 0.199
Expression system: Escherichia coli

Quick links

Citations

11 review citations

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

2 mentions without citation

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