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1p4f
From Proteopedia
| 1p4f, resolution 1.90Å () | |||||||||
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| Ligands: | |||||||||
| Gene: | DAPK1 OR DAPK (Homo sapiens) | ||||||||
| Domains: | S_TKc | ||||||||
| Related: | 1ig1, 1jkk, 1jkl, 1jks, 1jkt | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
DEATH ASSOCIATED PROTEIN KINASE CATALYTIC DOMAIN WITH BOUND INHIBITOR FRAGMENT
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1P4F is a 1 chain structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Velentza AV, Wainwright MS, Zasadzki M, Mirzoeva S, Schumacher AM, Haiech J, Focia PJ, Egli M, Watterson DM. An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury. Bioorg Med Chem Lett. 2003 Oct 20;13(20):3465-70. PMID:14505650
Page seeded by OCA on Mon Feb 16 20:09:23 2009
