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]

Structure

x-ray diffraction · 2 distinct chains · 45% helix, 16% strand (DSSP).

Ligands and binding sites

• 5JJ · N~6~-(2,6-dichlorophenyl)-N~6~-(pent-2-yn-1-yl) quinoline-4,6-diamine · ligand · 2 copies · chains A, B
• 5JT · (3R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-amine · ligand · 2 copies · chains A, B
• TLA · L(+)-tartaric acid · additive · chains A

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

7 pockets found on a 1 Å grid, 4 with a druggability of 0.5 or more.

Interfaces

1 interface between chains.

• A–B · 1632 Ų buried · 21 hydrogen bonds · protein-protein

Compared structures

• 5MW3 · Crystal structure of Dot1L in complex with inhibitor CPD1… · the same entry in another collection · chain A against A, TM-score 1.00
• Q8TEK3 · AlphaFold monomer V2.0 prediction for histone-lysine N-methyltransferase, H3 lysine-79… · a predicted model of the same protein · chain A against A, TM-score 0.94

Analyse

• Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
• Every structure of UniProt Q8TEK3
• Elsewhere: RCSB PDB 5MW3 · PDBe 5MW3 · UniProt Q8TEK3