1u6e

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Revision as of 01:45, 21 November 2007

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spinqualitylabelsall models 1u6e, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

1.85 Angstrom Crystal Structure of the C112A Mutant of Mycobacterium Tuberculosis Beta-Ketoacyl-Acyl Carrier Protein Synthase III (FabH)

Overview

Beta-ketoacyl-acyl carrier protein synthase III (FabH) catalyzes a two, step reaction that initiates the pathway of fatty acid biosynthesis in, plants and bacteria. In Mycobacterium tuberculosis, FabH catalyzes, extension of lauroyl, myristoyl and palmitoyl groups from which cell wall, mycolic acids of the bacterium are formed. The first step of the reaction, is an acyl group transfer from acyl-coenzyme A to the active-site cysteine, of the enzyme; the second step is acyl chain extension by two carbon atoms, through Claisen condensation with malonyl-acyl carrier protein. We have, previously determined the crystal structure of a type II, dissociated, M.tuberculosis FabH, which catalyzes extension of lauroyl, myristoyl and, palmitoyl groups. Here we describe the first long-chain Michaelis, substrate complex of a FabH, that of lauroyl-coenzyme A with a, catalytically disabled Cys-->Ala mutant of M.tuberculosis FabH. An, elongated channel extending from the mutated active-site cysteine defines, the acyl group binding locus that confers unique acyl substrate, specificity on M.tuberculosis FabH. CoA lies in a second channel, bound, primarily through interactions of its nucleotide group at the enzyme, surface. The apparent weak association of CoA in this complex may play a, role in the binding and dissociation of long chain acyl-CoA substrates and, products and poses questions pertinent to the mechanism of this enzyme.

About this Structure

1U6E is a Single protein structure of sequence from Mycobacterium tuberculosis with CL as ligand. Active as Beta-ketoacyl-acyl-carrier-protein synthase I, with EC number 2.3.1.41 Full crystallographic information is available from OCA.

Reference

Crystal structure of a substrate complex of Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III (FabH) with lauroyl-coenzyme A., Musayev F, Sachdeva S, Scarsdale JN, Reynolds KA, Wright HT, J Mol Biol. 2005 Mar 11;346(5):1313-21. Epub 2005 Jan 20. PMID:15713483[[Category: 3-oxoacyl-[acyl-carrier-protein] synthase iii]]

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