1w66: Difference between revisions

Revision as of 19:22, 18 December 2007

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 DKA 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

Page seeded by OCA on Tue Dec 18 18:31:56 2007

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OCA

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-<applet load="1w66" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1w66, resolution 1.08&Aring;" />
 '''STRUCTURE OF A LIPOATE-PROTEIN LIGASE B FROM MYCOBACTERIUM TUBERCULOSIS'''<br />
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 ==About this Structure==
-W66 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with DKA as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1W66 OCA].
+W66 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with DKA as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=AC1:Dka Binding Site For Chain A'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1W66 OCA].
 ==Reference==
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 [[Category: xmtb]]
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