Identification of a buried pocket for potent and selective inhibition of CHK1: prediction and verification

Structure

x-ray diffraction · 1 distinct chain · 33% helix, 21% strand (DSSP).

Ligands and binding sites

• ABO · 4-[3-(1H-benzimidazol-2-yl)-1H-indazol-6-yl]-2-methoxyphenol · ligand · chains A

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

Pockets

1 pocket found on a 1 Å grid, 1 with a druggability of 0.5 or more.

Compared structures

• 2C3K · Identification of a buried pocket for potent and selective inhibition of Chk1: prediction… · an experimental structure of the same protein · chain A against A, TM-score 1.00
• 1IA8 · The 1.7 a crystal structure of human cell cycle checkpoint kinase CHK1 · an experimental structure of the same protein · chain A against A, TM-score 1.00
• 2X8D · Discovery of a novel class of triazolones as checkpoint kinase inhibitors - hit to lead… · an experimental structure of the same protein · chain A against A, TM-score 1.00
• 2X8D · Discovery of a Novel Class of triazolones as Checkpoint Kinase Inhibitors - Hit to Lead… · an experimental structure of the same protein · chain A against A, TM-score 1.00
• 2YDI · Discovery of checkpoint kinase inhibitor AZD7762 by structure based design and… · an experimental structure of the same protein · chain A against A, TM-score 0.99
• 2YDI · Discovery of Checkpoint Kinase Inhibitor AZD7762 by Structure Based Design and… · an experimental structure of the same protein · chain A against A, TM-score 0.99
• 2HXL · Crystal structure of CHEK1 in complex with inhibitor 1 · an experimental structure of the same protein · chain A against A, TM-score 0.99
• 2HXL · crystal structure of Chek1 in complex with inhibitor 1 · an experimental structure of the same protein · chain A against A, TM-score 0.99
• 1ZYS · Co-crystal structure of Checkpoint Kinase Chk1 with a pyrrolo-pyridine inhibitor · an experimental structure of the same protein · chain A against A, TM-score 0.99
• 2HXQ · crystal structure of Chek1 in complex with inhibitor 2 · an experimental structure of the same protein · chain A against A, TM-score 0.99
• 2HXQ · Crystal structure of CHEK1 in complex with inhibitor 2 · an experimental structure of the same protein · chain A 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 O14757
• Elsewhere: RCSB PDB 2C3K · PDBe 2C3K · UniProt O14757 · AlphaFold DB O14757