1esm
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(New page: 200px<br /><applet load="1esm" size="450" color="white" frame="true" align="right" spinBox="true" caption="1esm, resolution 2.5Å" /> '''STRUCTURAL BASIS FOR ...)
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Revision as of 12:09, 20 November 2007
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STRUCTURAL BASIS FOR THE FEEDBACK REGULATION OF ESCHERICHIA COLI PANTOTHENATE KINASE BY COENZYME A
Overview
Pantothenate kinase (PanK) is a key regulatory enzyme in the coenzyme A, (CoA) biosynthetic pathway and catalyzes the phosphorylation of, pantothenic acid to form phosphopantothenate. CoA is a feedback inhibitor, of PanK activity by competitive binding to the ATP site. The structures of, the Escherichia coli enzyme, in complex with a nonhydrolyzable analogue of, ATP, 5'-adenylimido-diphosphate (AMPPNP), or with CoA, were determined at, 2.6 and 2.5 A, respectively. Both structures show that two dimers occupy, an asymmetric unit; each subunit has a alpha/beta mononucleotide-binding, fold with an extensive antiparallel coiled coil formed by two long helices, along the dimerization interface. The two ligands, AMPPNP and CoA, associate with PanK in very different ways, but their phosphate binding, sites overlap, explaining the kinetic competition between CoA and ATP., Residues Asp(127), His(177), and Arg(243) are proposed to be involved in, catalysis, based on modeling of the pentacoordinate transition state. The, more potent inhibition by CoA, compared with the CoA thioesters, is, explained by a tight interaction of the CoA thiol group with the side, chains of aromatic residues, which is predicted to discriminate against, the CoA thioesters. The PanK structure provides the framework for a more, detailed understanding of the mechanism of catalysis and feedback, regulation of PanK.
About this Structure
1ESM is a Single protein structure of sequence from Escherichia coli with COA as ligand. Active as Pantothenate kinase, with EC number 2.7.1.33 Full crystallographic information is available from OCA.
Reference
Structural basis for the feedback regulation of Escherichia coli pantothenate kinase by coenzyme A., Yun M, Park CG, Kim JY, Rock CO, Jackowski S, Park HW, J Biol Chem. 2000 Sep 8;275(36):28093-9. PMID:10862768
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