1w66

From Proteopedia

Revision as of 16:22, 18 December 2007

STRUCTURE OF A LIPOATE-PROTEIN LIGASE B FROM MYCOBACTERIUM TUBERCULOSIS

Overview

Lipoic acid is essential for the activation of a number of protein, complexes involved in key metabolic processes. Growth of Mycobacterium, tuberculosis relies on a pathway in which the lipoate attachment group is, synthesized from an endogenously produced octanoic acid moiety. In, patients with multiple-drug-resistant M. tuberculosis, expression of one, gene from this pathway, lipB, encoding for octanoyl-[acyl carrier, protein]-protein acyltransferase is considerably up-regulated, thus making, it a potential target in the search for novel antiinfectives against, tuberculosis. Here we present the crystal structure of the M. tuberculosis, LipB protein at atomic resolution, showing an unexpected thioether-linked, active-site complex with decanoic acid. We provide evidence that the, transferase functions as a cysteine/lysine dyad acyltransferase, in which, two invariant residues (Lys-142 and Cys-176) are likely to function as, acid/base catalysts. Analysis by MS reveals that the LipB catalytic, reaction proceeds by means of an internal thioesteracyl intermediate., Structural comparison of LipB with lipoate protein ligase A indicates, that, despite conserved structural and sequence active-site features in, the two enzymes, 4'-phosphopantetheine-bound octanoic acid recognition is, a specific property of LipB.

About this Structure

1W66 is a Single protein structure of sequence from Mycobacterium tuberculosis with DKA as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

The Mycobacterium tuberculosis LipB enzyme functions as a cysteine/lysine dyad acyltransferase., Ma Q, Zhao X, Nasser Eddine A, Geerlof A, Li X, Cronan JE, Kaufmann SH, Wilmanns M, Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8662-7. Epub 2006 May 30. PMID:16735476

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