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| - | [[Image:2i0e.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:2i0e.png|left|200px]] |
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| | {{STRUCTURE_2i0e| PDB=2i0e | SCENE= }} | | {{STRUCTURE_2i0e| PDB=2i0e | SCENE= }} |
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| - | '''Structure of catalytic domain of human protein kinase C beta II complexed with a bisindolylmaleimide inhibitor'''
| + | ===Structure of catalytic domain of human protein kinase C beta II complexed with a bisindolylmaleimide inhibitor=== |
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| - | ==Overview==
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| - | The conventional protein kinase C isoform, PKCII, is a signaling kinase activated during the hyperglycemic state and has been associated with the development of microvascular abnormalities associated with diabetes. PKCII, therefore, has been identified as a therapeutic target where inhibitors of its kinase activity are being pursued for treatment of microvascular-related diabetic complications. In this report, we describe the crystal structure of the catalytic domain of PKCbetaII complexed with an inhibitor at 2.6 A resolution. The kinase domain of PKCbetaII was cleaved and purified from full-length PKCbetaII expressed in baculovirus-infected insect cells. The overall kinase domain structure follows the classical bilobal fold and is in its fully activated conformation with three well-defined phosphorylated residues: Thr-500, Thr-641, and Ser-660. Different from the crystal structures of nonconventional PKC isoforms, the C-terminus of the PKCbetaII catalytic domain is almost fully ordered and features a novel alpha helix in the turn motif. An ATP-competitive inhibitor, 2-methyl-1H-indol-3-yl-BIM-1, was crystallized with the PKCbetaII catalytic domain as a dimer of two enzyme-inhibitor complexes. The bound inhibitor adopts a nonplanar conformation in the ATP-binding site, with the kinase domain taking on an intermediate, open conformation. This PKCbetaII-inhibitor complex represents the first structural description of any conventional PKC kinase domain. Given the pathogenic role of PKCbetaII in the development of diabetic complications, this structure can serve as a template for the rational design of inhibitors as potential therapeutic agents. | + | The line below this paragraph, {{ABSTRACT_PUBMED_17115692}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17115692 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17115692}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Protein kinase c beta ii]] | | [[Category: Protein kinase c beta ii]] |
| | [[Category: Serine/threonine protein kinase]] | | [[Category: Serine/threonine protein kinase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:55:41 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:17:37 2008'' |
Revision as of 03:17, 29 July 2008
Template:STRUCTURE 2i0e
Structure of catalytic domain of human protein kinase C beta II complexed with a bisindolylmaleimide inhibitor
Template:ABSTRACT PUBMED 17115692
About this Structure
2I0E is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of the catalytic domain of human protein kinase C beta II complexed with a bisindolylmaleimide inhibitor., Grodsky N, Li Y, Bouzida D, Love R, Jensen J, Nodes B, Nonomiya J, Grant S, Biochemistry. 2006 Nov 28;45(47):13970-81. PMID:17115692
Page seeded by OCA on Tue Jul 29 06:17:37 2008
