1P4F

DEATH ASSOCIATED PROTEIN KINASE CATALYTIC DOMAIN WITH BOUND INHIBITOR FRAGMENT

Summary for 1P4F

• Entry DOI: 10.2210/pdb1p4f/pdb
• Related: 1IG1 1JKK 1JKL 1JKS 1JKT
• Descriptor: Death-associated protein kinase 1, 5,6-Dihydro-benzo[H]cinnolin-3-ylamine (3 entities in total)
• Functional Keywords: transferase, kinase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 33862.42

Authors

Velentza, A.V.,Wainwright, M.S.,Zasadzki, M.,Mirzoeva, S.,Haiech, J.,Focia, P.J.,Egli, M.,Watterson, D.M. (deposition date: 2003-04-23, release date: 2004-09-28, Last modification date: 2023-08-16)

Primary citation

Velentza, A.V.,Wainwright, M.S.,Zasadzki, M.,Mirzoeva, S.,Schumacher, A.M.,Haiech, J.,Focia, P.J.,Egli, M.,Watterson, D.M.
An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury.
Bioorg.Med.Chem.Lett., 13:3465-3470, 2003

PubMed Abstract: 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.

PubMed: 14505650
DOI: 10.1016/S0960-894X(03)00733-9

Experimental method

X-RAY DIFFRACTION (1.9 Å)