1gkz
From Proteopedia
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==Overview== | ==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. ... | + | 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== | ==About this Structure== | ||
| - | 1GKZ is a | + | 1GKZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with MG, K, CL, XE and ADP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.4 Transferred entry: 2.7.11.4], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.115 2.7.1.115] Structure known Active Site: K. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GKZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: potassium]] | [[Category: potassium]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 12:31:02 2007'' |
Revision as of 10:25, 5 November 2007
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BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE KINASE (BCK) COMPLXED WITH ADP
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
1GKZ is a Single protein structure of sequence from Rattus norvegicus with MG, K, CL, XE and ADP as ligands. Active as Transferred entry: 2.7.11.4, with EC number 2.7.1.115 Structure known Active Site: K. 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 Mon Nov 5 12:31:02 2007
Categories: Rattus norvegicus | Single protein | Transferred entry: 2.7.11.4 | Chuang, D.T. | Chuang, J.L. | Machius, M. | Tomchick, D.R. | Wynn, R.M. | ADP | CL | K | MG | XE | Mitochondrial protein kinase | Potassium
