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

Structure

x-ray diffraction · 2 distinct chains · 48% helix, 10% strand (DSSP).

Ligands and binding sites

• C35 · N~2~-{[1-(4-chlorophenyl)-5-methyl-1H-1,2,4-triazol-3-yl]carbonyl}-N~5~-(diaminomethylidene)-L-ornithyl-L-leucyl-L-isoleucyl-4-fluoro-L-phenylalaninamide · ligand · 2 copies · chains B, D

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

Pockets

14 pockets found on a 1 Å grid, 10 with a druggability of 0.5 or more.

Interfaces

5 interfaces between chains.

• A–B · 1757 Ų buried · 19 hydrogen bonds · protein-protein
• C–D · 1722 Ų buried · 24 hydrogen bonds · protein-protein
• B–C · 512 Ų buried · 3 hydrogen bonds · protein-protein
• A–D · 440 Ų buried · 3 hydrogen bonds · protein-protein
• A–C · 123 Ų buried · 1 hydrogen bond · protein-protein

Compared structures

• 2V22 · REPLACE: A strategy for Iterative Design of Cyclin Binding Groove Inhibitors · the same entry in another collection · chain D against D, 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 C 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 2V22 · PDBe 2V22 · UniProt P24941 · UniProt P20248