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1p4f
From Proteopedia
(New page: 200px<br /> <applet load="1p4f" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p4f, resolution 1.90Å" /> '''DEATH ASSOCIATED PR...) |
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| - | [[Image:1p4f.gif|left|200px]]<br /> | + | [[Image:1p4f.gif|left|200px]]<br /><applet load="1p4f" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1p4f" size=" | + | |
caption="1p4f, resolution 1.90Å" /> | caption="1p4f, resolution 1.90Å" /> | ||
'''DEATH ASSOCIATED PROTEIN KINASE CATALYTIC DOMAIN WITH BOUND INHIBITOR FRAGMENT'''<br /> | '''DEATH ASSOCIATED PROTEIN KINASE CATALYTIC DOMAIN WITH BOUND INHIBITOR FRAGMENT'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Death associated protein kinase (DAPK) is a calcium and calmodulin | + | 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== | ==About this Structure== | ||
| - | 1P4F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with DRG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1P4F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=DRG:'>DRG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P4F OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Egli, M.]] | [[Category: Egli, M.]] | ||
| - | [[Category: Focia, P | + | [[Category: Focia, P J.]] |
[[Category: Haiech, J.]] | [[Category: Haiech, J.]] | ||
[[Category: Mirzoeva, S.]] | [[Category: Mirzoeva, S.]] | ||
| - | [[Category: Velentza, A | + | [[Category: Velentza, A V.]] |
| - | [[Category: Wainwright, M | + | [[Category: Wainwright, M S.]] |
| - | [[Category: Watterson, D | + | [[Category: Watterson, D M.]] |
[[Category: Zasadzki, M.]] | [[Category: Zasadzki, M.]] | ||
[[Category: DRG]] | [[Category: DRG]] | ||
| Line 26: | Line 25: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:24:57 2008'' |
Revision as of 12:24, 21 February 2008
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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 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 Thu Feb 21 14:24:57 2008
