Replace: a strategy for iterative design of cyclin binding groove inhibitors

Structure

x-ray diffraction · 3 distinct chains · 49% helix, 10% strand (DSSP).

Ligands and binding sites

• MTZ · 4-methyl-5-{(2E)-2-[(4-morpholin-4-ylphenyl)imino]-2,5-dihydropyrimidin-4-yl}-1,3-thiazol-2-amine · ligand · 2 copies · chains A, C
• GVC · 1-(3,5-dichlorophenyl)-5-methyl-1H-1,2,4-triazole-3-carboxylic acid · ligand · 2 copies · chains B, E, D, F
• NH2 · Amino group · ion · 2 copies · chains B, E, D, F

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

Pockets

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

Interfaces

7 interfaces between chains.

• A–B · 1745 Ų buried · 18 hydrogen bonds · protein-protein
• C–D · 1711 Ų buried · 24 hydrogen bonds · protein-protein
• B–C · 516 Ų buried · 3 hydrogen bonds · protein-protein
• A–D · 480 Ų buried · 2 hydrogen bonds · protein-protein
• D–F · 360 Ų buried · 3 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 2 covalent, 2 modified (covalent ligand, nonstandard).

Compared structures

• 2UUE · REPLACE: A strategy for Iterative Design of Cyclin Binding Groove Inhibitors · the same entry in another collection · chain F against F, TM-score 1.00
• P20248 · AlphaFold monomer V2.0 prediction for cyclin-A2 (P20248) · a predicted model of the same protein · chain B against A, TM-score 1.00
• P24941 · AlphaFold monomer V2.0 prediction for cyclin-dependent kinase 2 (P24941) · a predicted model of the same protein · chain A against A, TM-score 0.91

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 P24941
• Every structure of UniProt P20248
• Elsewhere: RCSB PDB 2UUE · PDBe 2UUE · UniProt P24941 · UniProt P20248