PDBsum entry: 1u6e

Transferase

PDB id: 1u6e

Contents

Protein chains

334 a.a. *

Metals

_CL ×4

Waters ×556

* Residue conservation analysis

PDB id:

1u6e

Name:

Transferase

Title:

1.85 angstrom crystal structure of the c112a mutant of mycob tuberculosis beta-ketoacyl-acyl carrier protein synthase ii

Structure:

3-oxoacyl-[acyl-carrier-protein] synthase iii. Chain: a, b. Synonym: beta-ketoacyl-acp synthase iii, kas iii, mtfabh. Engineered: yes. Mutation: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: fabh. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

1.85Å R-factor: 0.183 R-free: 0.206

Authors:

F.Mussayev,S.Sachedeva,J.N.Scarsdale,K.A.Reynolds,H.T.Wright

Key ref:

F.Musayev et al. (2005). Crystal structure of a substrate complex of Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III (FabH) with lauroyl-coenzyme A. J Mol Biol, 346, 1313-1321. PubMed id: 15713483 DOI: 10.1016/j.jmb.2004.12.044

Date:

29-Jul-04 Release date: 24-May-05

Protein chains

P0A574  (FABH_MYCTU) -  3-oxoacyl-[acyl-carrier-protein] synthase 3

Seq: 335 a.a.

Struc: 334 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.3.1.180 - Beta-ketoacyl-acyl-carrier-protein synthase Iii.
• Reaction: Acetyl-CoA + malonyl-[acyl-carrier-protein] = acetoacetyl-[acyl-carrier- protein] + CoA + CO₂

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (1 term)
• Biological process: metabolic process (5 terms)
• Biochemical function: catalytic activity (9 terms)

reference

DOI no: 10.1016/j.jmb.2004.12.044

J Mol Biol 346:1313-1321 (2005)

PubMed id: 15713483

Crystal structure of a substrate complex of Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III (FabH) with lauroyl-coenzyme A.

F.Musayev, S.Sachdeva, J.N.Scarsdale, K.A.Reynolds, H.T.Wright.

ABSTRACT

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.

Selected figure(s)

Figure 1.
Figure 1. Mechanism for the FabH catalyzed initiation of fatty acid biosynthesis. The intermediate enclosed in a box represents the Michaelis complex whose structure for the C112A mutant is described here.

Figure 2.
Figure 2. Composite omit map electron density for lauroyl-CoA bound to subunit A of mtFabH homodimer. Electron density is contoured at 1s.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 346, 1313-1321) copyright 2005.

Figures were selected by an automated process.