2i0e: Difference between revisions
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|PDB= 2i0e |SIZE=350|CAPTION= <scene name='initialview01'>2i0e</scene>, resolution 2.60Å | |PDB= 2i0e |SIZE=350|CAPTION= <scene name='initialview01'>2i0e</scene>, resolution 2.60Å | ||
|SITE= | |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> | |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>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2i0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i0e OCA], [http://www.ebi.ac.uk/pdbsum/2i0e PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2i0e RCSB]</span> | |||
}} | }} | ||
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[[Category: Grodsky, N B.]] | [[Category: Grodsky, N B.]] | ||
[[Category: Love, R L.]] | [[Category: Love, R L.]] | ||
[[Category: protein kinase c]] | [[Category: protein kinase c]] | ||
[[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 | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:38:00 2008'' | ||
Revision as of 03:38, 31 March 2008
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| , resolution 2.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Activity: | Protein kinase C, with EC number 2.7.11.13 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of catalytic domain of human protein kinase C beta II complexed with a bisindolylmaleimide inhibitor
OverviewOverview
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 StructureAbout this Structure
2I0E is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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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