Novel Modes of Inhibition of Wild-Type IDH1: Direct Covalent Modification of His315 with Cmpd13

Structure

x-ray diffraction · resolution 2.02 · 1 distinct chain · 47% helix, 22% strand (DSSP).

Ligands and binding sites

• ICT · Isocitric acid · ligand · 3 copies · chains B, A, C
• DWG · (6aS,7S,9S,10aS)-7-methyl-8-oxo-10a-phenyl-2-(phenylamino)-5,6,6a,7,8,9,10,10a-octahydrobenzo[h]quinazoline-9-carbonitrile · ligand · 3 copies · chains B, C, A
• CA · Calcium ion · metal · 3 copies · chains B, A, C

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

Pockets

13 pockets found on a 1 Å grid, 2 with a druggability of 0.5 or more.

Interfaces

3 interfaces between chains.

• B–A · 3616 Ų buried · 61 hydrogen bonds · protein-protein
• B–C · 182 Ų buried · 2 hydrogen bonds · protein-protein
• C–A · 29 Ų buried · 0 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 1 covalent (covalent ligand).

Compared structures

• 6BL1 · Novel modes of inhibition of wild-type IDH1: direct covalent modification of HIS315 with… · the same entry in another collection · chain A against A, TM-score 1.00
• O75874 · AlphaFold monomer V2.0 prediction for isocitrate dehydrogenase [NADP] cytoplasmic (O75874) · a predicted model of the same protein · chain B against A, TM-score 0.96

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 O75874
• Elsewhere: RCSB PDB 6BL1 · PDBe 6BL1 · UniProt O75874