1u1z

From Proteopedia

Revision as of 06:59, 18 November 2007

The Structure of (3R)-hydroxyacyl-ACP dehydratase (FabZ)

Overview

Type II fatty acid biosynthesis systems are essential for membrane, formation in bacteria, making the constituent proteins of this pathway, attractive targets for antibacterial drug discovery. The third step in the, elongation cycle of the type II fatty acid biosynthesis is catalyzed by, beta-hydroxyacyl-(acyl carrier protein) (ACP) dehydratase. There are two, isoforms. FabZ, which catalyzes the dehydration of (3R)-hydroxyacyl-ACP to, trans-2-acyl-ACP, is a universally expressed component of the bacterial, type II system. FabA, the second isoform, as has more limited distribution, in nature and, in addition to dehydration, also carries out the, isomerization of trans-2- to cis-3-decenoyl-ACP as an essential step in, unsaturated fatty acid biosynthesis. We report the structure of FabZ from, the important human pathogen Pseudomonas aeruginosa at 2.5 A of, resolution. PaFabZ is a hexamer (trimer of dimers) with the His/Glu, catalytic dyad located within a deep, narrow tunnel formed at the dimer, interface. Site-directed mutagenesis experiments showed that the obvious, differences in the active site residues that distinguish the FabA and FabZ, subfamilies of dehydratases do not account for the unique ability of FabA, to catalyze isomerization. Because the catalytic machinery of the two, enzymes is practically indistinguishable, the structural differences, observed in the shape of the substrate binding channels of FabA and FabZ, lead us to hypothesize that the different shapes of the tunnels control, the conformation and positioning of the bound substrate, allowing FabA, but not FabZ, to catalyze the isomerization reaction.

About this Structure

1U1Z is a Single protein structure of sequence from Pseudomonas aeruginosa with SO4 as ligand. The following page contains interesting information on the relation of 1U1Z with [Fatty Acid Synthase]. Full crystallographic information is available from OCA.

Reference

The structure of (3R)-hydroxyacyl-acyl carrier protein dehydratase (FabZ) from Pseudomonas aeruginosa., Kimber MS, Martin F, Lu Y, Houston S, Vedadi M, Dharamsi A, Fiebig KM, Schmid M, Rock CO, J Biol Chem. 2004 Dec 10;279(50):52593-602. Epub 2004 Sep 14. PMID:15371447

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