1gkx
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(New page: 200px<br /><applet load="1gkx" size="450" color="white" frame="true" align="right" spinBox="true" caption="1gkx, resolution 2.30Å" /> '''BRANCHED-CHAIN ALPHA...)
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Revision as of 14:00, 20 November 2007
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BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE KINASE (BCK)
Overview
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.
About this Structure
1GKX is a Single protein structure of sequence from Rattus norvegicus with CL as ligand. Active as [3-methyl-2-oxobutanoate_dehydrogenase_(acetyl-transferring)_kinase [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase], with EC number 2.7.11.4 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[[Category: [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase]]
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