Differential binding of inhibitors to active and inactive CDK2 provides insights for drug design

Structure

x-ray diffraction · 3 distinct chains · 48% helix, 8% strand (DSSP).

Ligands and binding sites

• CK4 · 4-(2,4-dimethyl-1,3-thiazol-5-yl)-N-[4-(trifluoromethyl)phenyl]pyrimidin-2-amine · ligand · 2 copies · chains A, C
• NH2 · Amino group · ion · 2 copies · chains F, D, H

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

Pockets

15 pockets found on a 1 Å grid, 9 with a druggability of 0.5 or more.

Interfaces

7 interfaces between chains.

• A–B · 1659 Ų buried · 17 hydrogen bonds · protein-protein
• C–D · 1607 Ų buried · 23 hydrogen bonds · protein-protein
• B–F · 553 Ų buried · 11 hydrogen bonds · protein-protein
• D–H · 520 Ų buried · 7 hydrogen bonds · protein-protein
• B–C · 477 Ų buried · 4 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 4 modified (nonstandard).

Compared structures

• 2C5V · Differential Binding Of Inhibitors To Active And Inactive Cdk2 Provides Insights For Drug… · the same entry in another collection · chain H against H, 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 0.92

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 2C5V · PDBe 2C5V · UniProt P24941 · UniProt P20248