2ix4

From Proteopedia

Revision as of 17:29, 18 December 2007

ARABIDOPSIS THALIANA MITOCHONDRIAL BETA-KETOACYL ACP SYNTHASE HEXANOIC ACID COMPLEX

Overview

Two distinct ways of organizing fatty acid biosynthesis exist: the, multifunctional type I fatty acid synthase (FAS) of mammals, fungi, and, lower eukaryotes with activities residing on one or two polypeptides; and, the dissociated type II FAS of prokaryotes, plastids, and mitochondria, with individual activities encoded by discrete genes. The beta-ketoacyl, [ACP] synthase (KAS) moiety of the mitochondrial FAS (mtKAS) is targeted, by the antibiotic cerulenin and possibly by the other antibiotics, inhibiting prokaryotic KASes: thiolactomycin, platensimycin, and the, alpha-methylene butyrolactone, C75. The high degree of structural, similarity between mitochondrial and prokaryotic KASes complicates, development of novel antibiotics targeting prokaryotic KAS without, affecting KAS domains of cytoplasmic FAS. KASes catalyze the C(2) fatty, acid elongation reaction using either a Cys-His-His or Cys-His-Asn, catalytic triad. Three KASes with different substrate specificities, participate in synthesis of the C(16) and C(18) products of prokaryotic, FAS. By comparison, mtKAS carries out all elongation reactions in the, mitochondria. We present the X-ray crystal structures of the, Cys-His-His-containing human mtKAS and its hexanoyl complex plus the, hexanoyl complex of the plant mtKAS from Arabidopsis thaliana. The, structures explain (1) the bimodal (C(6) and C(10)-C(12)) substrate, preferences leading to the C(8) lipoic acid precursor and long chains for, the membranes, respectively, and (2) the low cerulenin sensitivity of the, human enzyme; and (3) reveal two different potential acyl-binding-pocket, extensions. Rearrangements taking place in the active site, including, subtle changes in the water network, indicate a change in cooperativity of, the active-site histidines upon primer binding.

About this Structure

2IX4 is a Single protein structure of sequence from Arabidopsis thaliana with K and 6NA as ligands. Active as Beta-ketoacyl-acyl-carrier-protein synthase I, with EC number 2.3.1.41 Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Structure of the human beta-ketoacyl [ACP] synthase from the mitochondrial type II fatty acid synthase., Christensen CE, Kragelund BB, von Wettstein-Knowles P, Henriksen A, Protein Sci. 2007 Feb;16(2):261-72. PMID:17242430

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