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| - | [[Image:1gjv.jpg|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1gjv| PDB=1gjv | SCENE= }} | | {{STRUCTURE_1gjv| PDB=1gjv | SCENE= }} |
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| - | '''BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE KINASE (BCK) COMPLXED WITH ATP-GAMMA-S'''
| + | ===BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE KINASE (BCK) COMPLXED WITH ATP-GAMMA-S=== |
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| - | ==Overview==
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| - | Mitochondrial protein kinases (mPKs) are molecular switches that down-regulate the oxidation of branched-chain alpha-ketoacids and pyruvate. Elevated levels of these metabolites are implicated in disease states such as insulin-resistant Type II diabetes, branched-chain ketoaciduria, and primary lactic acidosis. We report a three-dimensional structure of a member of the mPK family, rat branched-chain alpha-ketoacid dehydrogenase kinase (BCK). BCK features a characteristic nucleotide-binding domain and a four-helix bundle domain. These two domains are reminiscent of modules found in protein histidine kinases (PHKs), which are involved in two-component signal transduction systems. Unlike PHKs, BCK dimerizes through direct interaction of two opposing nucleotide-binding domains. Nucleotide binding to BCK is uniquely mediated by both potassium and magnesium. Binding of ATP induces disorder-order transitions in a loop region at the nucleotide-binding site. These structural changes lead to the formation of a quadruple aromatic stack in the interface between the nucleotide-binding domain and the four-helix bundle domain, where they induce a movement of the top portion of two helices. Phosphotransfer induces further ordering of the loop region, effectively trapping the reaction product ADP, which explains product inhibition in mPKs. The BCK structure is a prototype for all mPKs and will provide a framework for structure-assisted inhibitor design for this family of kinases.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_11562470}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 11562470 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_11562470}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Potassium]] | | [[Category: Potassium]] |
| | [[Category: Transferase]] | | [[Category: Transferase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:40:01 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 05:24:33 2008'' |
Revision as of 02:24, 1 July 2008
Template:STRUCTURE 1gjv
BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE KINASE (BCK) COMPLXED WITH ATP-GAMMA-S
Template:ABSTRACT PUBMED 11562470
About this Structure
1GJV is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Structure of rat BCKD kinase: nucleotide-induced domain communication in a mitochondrial protein kinase., Machius M, Chuang JL, Wynn RM, Tomchick DR, Chuang DT, Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11218-23. Epub 2001 Sep 18. PMID:11562470
Page seeded by OCA on Tue Jul 1 05:24:33 2008
