Identification of a new class of potent CDC7 inhibitors designed by putative pharmacophore model: synthesis and biological evaluation of 2,3-DIHYDROTHIENO[3,2-D]PYRIMIDIN-4(1H)-ones

Structure

x-ray diffraction · 2 distinct chains · 39% helix, 14% strand (DSSP).

Ligands and binding sites

• 81G · (1s,4s)-4-(4-fluorophenyl)-4-hydroxy-6'-(5-methyl-1H-pyrazol-4-yl)-1'H-spiro[cyclohexane-1,2'-thieno[3,2-d]pyrimidin]-4'(3'H)-one · ligand · 4 copies · chains A, B, C, D

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

Pockets

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

Interfaces

6 interfaces between chains.

• B–C · 1918 Ų buried · 12 hydrogen bonds · protein-protein
• A–D · 1910 Ų buried · 20 hydrogen bonds · protein-protein
• A–C · 971 Ų buried · 8 hydrogen bonds · protein-protein
• B–D · 956 Ų buried · 5 hydrogen bonds · protein-protein
• A–B · 268 Ų buried · 2 hydrogen bonds · protein-protein

Compared structures

• 5U7R · Identification of A New Class of Potent Cdc7 Inhibitors Designed by Putative… · the same entry in another collection · chain A against A, TM-score 1.00
• O75116 · AlphaFold monomer V2.0 prediction for rho-associated protein kinase 2 (O75116) · a predicted model of the same protein · chain D against A, TM-score 0.99

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 O75116
• Elsewhere: RCSB PDB 5U7R · PDBe 5U7R · UniProt O75116