| http://purl.uniprot.org/citations/17115692 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17115692 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17115692 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.org/dc/terms/identifier | "doi:10.1021/bi061128h"xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.org/dc/terms/identifier | "doi:10.1021/bi061128h"xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Li Y."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Li Y."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Love R."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Love R."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Grant S."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Grant S."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Jensen J."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Jensen J."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Bouzida D."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Bouzida D."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Grodsky N."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Grodsky N."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Nodes B."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Nodes B."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Nonomiya J."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/author | "Nonomiya J."xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/name | "Biochemistry"xsd:string |
| http://purl.uniprot.org/citations/17115692 | http://purl.uniprot.org/core/name | "Biochemistry"xsd:string |