2c3k is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Inhibition of the Chk1 kinase by small molecules binding to its active site is a strategy of great therapeutic interest for oncology. We report how computational modelling predicted the binding mode of ligands of special interest to the Chk1 ATP site, for representatives of an indazole series and debromohymenialdisine. These binding modes were subsequently confirmed by X-ray crystallography. The binding mode of a potent indazole derivative involves non-conventional C-H...O and N-H...pi-aromatic interactions with the protein. These interactions are formed in a buried pocket at the periphery of the ATP-binding site, the importance of which has previously been overlooked for ligand design against Chk1. It is demonstrated that filling this pocket can confer ligands with dramatically enhanced affinity for Chk1. Structural arguments in conjunction with assay data explain why targeting this pocket is also advantageous for selective binding to Chk1. Structural overlays of known inhibitors complexed with Chk1 show that only the indazole series utilizes the pocket of interest. Therefore, the analysis presented here should prove helpful in guiding future structure-based ligand design efforts against Chk1.
Identification of a buried pocket for potent and selective inhibition of Chk1: prediction and verification.,Foloppe N, Fisher LM, Francis G, Howes R, Kierstan P, Potter A Bioorg Med Chem. 2006 Mar 15;14(6):1792-804. Epub 2005 Nov 9. PMID:16289938[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑Foloppe N, Fisher LM, Francis G, Howes R, Kierstan P, Potter A. Identification of a buried pocket for potent and selective inhibition of Chk1: prediction and verification. Bioorg Med Chem. 2006 Mar 15;14(6):1792-804. Epub 2005 Nov 9. PMID:16289938 doi:10.1016/j.bmc.2005.10.022
