1p4f: Difference between revisions

Revision as of 15:24, 21 February 2008

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 with as ligand. 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

Page seeded by OCA on Thu Feb 21 14:24:57 2008

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OCA

@@ Line 1: / Line 1: @@
-[[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="450" color="white" frame="true" align="right" spinBox="true"
 caption="1p4f, resolution 1.90&Aring;" />
 '''DEATH ASSOCIATED PROTEIN KINASE CATALYTIC DOMAIN WITH BOUND INHIBITOR FRAGMENT'''<br />
 ==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.
+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==
-P4F 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1P4F OCA].
+P4F 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==
@@ Line 15: / Line 14: @@
 [[Category: Single protein]]
 [[Category: Egli, M.]]
-[[Category: Focia, P.J.]]
+[[Category: Focia, P J.]]
 [[Category: Haiech, J.]]
 [[Category: Mirzoeva, S.]]
-[[Category: Velentza, A.V.]]
+[[Category: Velentza, A V.]]
-[[Category: Wainwright, M.S.]]
+[[Category: Wainwright, M S.]]
-[[Category: Watterson, D.M.]]
+[[Category: Watterson, D M.]]
 [[Category: Zasadzki, M.]]
 [[Category: DRG]]
@@ Line 26: / Line 25: @@
 [[Category: transferase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:39:54 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:24:57 2008''