1p4f
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| , resolution 1.90Å | |||||||
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| Ligands: | |||||||
| Gene: | DAPK1 OR DAPK (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
DEATH ASSOCIATED PROTEIN KINASE CATALYTIC DOMAIN WITH BOUND INHIBITOR FRAGMENT
OverviewOverview
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 StructureAbout this Structure
1P4F is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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
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