1U6E

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

Summary for 1U6E

• Entry DOI: 10.2210/pdb1u6e/pdb
• Related: 1EBL 1HNJ 1HZP
• Descriptor: 3-oxoacyl-[acyl-carrier-protein] synthase III, CHLORIDE ION (3 entities in total)
• Functional Keywords: transferase, 3-oxoacyl-[acyl-carrier-protein] synthase iii
• Biological source: Mycobacterium tuberculosis
• Cellular location: Cytoplasm: P0A574
• Total number of polymer chains: 2
• Total formula weight: 69884.46

Authors

Mussayev, F.,Sachedeva, S.,Scarsdale, J.N.,Reynolds, K.A.,Wright, H.T. (deposition date: 2004-07-29, release date: 2005-05-24, Last modification date: 2023-08-23)

Primary citation

Musayev, F.,Sachdeva, S.,Scarsdale, J.N.,Reynolds, K.A.,Wright, H.T.
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, 2005

PubMed 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.

PubMed: 15713483
DOI: 10.1016/j.jmb.2004.12.044

Experimental method

X-RAY DIFFRACTION (1.85 Å)