› 5mw3

X-ray diffraction
2.09Å resolution

Crystal structure of Dot1L in complex with inhibitor CPD1 [N6-(2,6-dichlorophenyl)-N6-(pent-2-yn-1-yl)quinoline-4,6-diamine] and inhibitor CPD2 [(R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-amine]

Released:
DOI: 10.2210/pdb5mw3/pdb
PDB entry 5mw3 coloured by chain, front view.
PDB entry 5mw3 coloured by chain, side view.
PDB entry 5mw3 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach.
Möbitz H, Machauer R, Holzer P, Vaupel A, Stauffer F, Ragot C, Caravatti G, Scheufler C, Fernandez C, Hommel U, Tiedt R, Beyer KS, Chen C, Zhu H, Gaul C
ACS Med Chem Lett 8 338-343 (2017)
PMID: 28337327

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

3 bound ligands:
Ligand 5JJ 2 x 5JJ
Ligand 5JT 2 x 5JT
Ligand TLA 1 x TLA
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P63
Unit cell:
a: 158.48Å b: 158.48Å c: 74.07Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.176 0.175 0.193
Expression system: Escherichia coli

Quick links

Citations

8 review citations

Chemical and Biochemical Perspectives of Protein Lysine Methylation.
Luo M. (2018)
7 more

4 mentions without citation

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