1w66
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STRUCTURE OF A LIPOATE-PROTEIN LIGASE B FROM MYCOBACTERIUM TUBERCULOSIS
OverviewOverview
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 StructureAbout this Structure
1W66 is a Single protein structure of sequence from Mycobacterium tuberculosis with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
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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OCA- Pages with broken file links
- Mycobacterium tuberculosis
- Single protein
- Ma, Q.
- Wilmanns, M.
- XMTB, Mycobacterium Tuberculosis Structural Proteomics Project.
- DKA
- Acyltransferase
- Lipoate-protein ligase b
- Lipoic acid
- Lipoyltransferase
- Mycobacterium tuberculosis structural proteomics project
- Structural genomics
- Transferase
- Xmtb