1p4f
From Proteopedia
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DEATH ASSOCIATED PROTEIN KINASE CATALYTIC DOMAIN WITH BOUND INHIBITOR FRAGMENT
Overview
Death associated protein kinase (DAPK) is a calcium and calmodulin, regulated enzyme that functions early in eukaryotic programmed cell death, or apoptosis. To validate DAPK as a potential drug discovery target for, acute brain injury, the first small molecule DAPK inhibitor was, synthesized and tested in vivo. A single injection of the, aminopyridazine-based inhibitor administered 6 h after injury attenuated, brain tissue or neuronal biomarker loss measured, respectively, 1 week and, 3 days later. Because aminopyridazine is a privileged structure in, neuropharmacology, we determined the high-resolution crystal structure of, a binary complex between the kinase domain and a molecular fragment of the, DAPK inhibitor. The co-crystal structure describes a structural basis for, interaction and provides a firm foundation for structure-assisted design, of lead compounds with appropriate molecular properties for future drug, development.
About this Structure
1P4F is a Single protein structure of sequence from Homo sapiens with DRG as ligand. Full crystallographic information is available from OCA.
Reference
An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury., Velentza AV, Wainwright MS, Zasadzki M, Mirzoeva S, Schumacher AM, Haiech J, Focia PJ, Egli M, Watterson DM, Bioorg Med Chem Lett. 2003 Oct 20;13(20):3465-70. PMID:14505650
Page seeded by OCA on Mon Nov 12 18:39:54 2007
