› 5dsx

X-ray diffraction
2.41Å resolution

Crystal structure of Dot1L in complex with inhibitor CPD10 [6'-chloro-1,4-dimethyl-5'-(2-methyl-6-((4-(methylamino)pyrimidin-2-yl)amino)-1H-indol-1-yl)-[3,3'-bipyridin]-2(1H)-one]

Released:
DOI: 10.2210/pdb5dsx/pdb
PDB entry 5dsx coloured by chain, front view.
PDB entry 5dsx coloured by chain, side view.
PDB entry 5dsx coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of Novel Dot1L Inhibitors through a Structure-Based Fragmentation Approach.
Chen C, Zhu H, Stauffer F, Caravatti G, Vollmer S, Machauer R, Holzer P, Möbitz H, Scheufler C, Klumpp M, Tiedt R, Beyer KS, Calkins K, Guthy D, Kiffe M, Zhang J, Gaul C
ACS Med Chem Lett 7 735-40 (2016)
PMID: 27563395

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

2 bound ligands:
Ligand K 2 x K
Ligand 5EW 2 x 5EW
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P63
Unit cell:
a: 158.14Å b: 158.14Å c: 73.98Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.173 0.172 0.202
Expression system: Escherichia coli

Quick links

Citations

18 review citations

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

3 mentions without citation

Methyltransferase Inhibitors: Competing with, or Exploiting the Bound Cofactor.
Ferreira de Freitas et al. (2019)
2 more