2i0e
From Proteopedia
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| - | [[Image:2i0e.gif|left|200px]] | + | [[Image:2i0e.gif|left|200px]] |
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| - | '''Structure of catalytic domain of human protein kinase C beta II complexed with a bisindolylmaleimide inhibitor''' | + | {{Structure |
| + | |PDB= 2i0e |SIZE=350|CAPTION= <scene name='initialview01'>2i0e</scene>, resolution 2.60Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=PDS:3-{1-[3-(DIMETHYLAMINO)PROPYL]-2-METHYL-1H-INDOL-3-YL}-4-(2-METHYL-1H-INDOL-3-YL)-1H-PYRROLE-2,5-DIONE'>PDS</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Protein_kinase_C Protein kinase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.13 2.7.11.13] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Structure of catalytic domain of human protein kinase C beta II complexed with a bisindolylmaleimide inhibitor''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2I0E is a [ | + | 2I0E is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I0E OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17115692 17115692] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein kinase C]] | [[Category: Protein kinase C]] | ||
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[[Category: serine/threonine protein kinase]] | [[Category: serine/threonine protein kinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:23:56 2008'' |
Revision as of 15:23, 20 March 2008
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| , resolution 2.60Å | |||||||
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| Ligands: | |||||||
| Activity: | Protein kinase C, with EC number 2.7.11.13 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of catalytic domain of human protein kinase C beta II complexed with a bisindolylmaleimide inhibitor
Overview
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.
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
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