1w66
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Lipoic acid is essential for the activation of a number of protein | + | 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== | ==About this Structure== | ||
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[[Category: Ma, Q.]] | [[Category: Ma, Q.]] | ||
[[Category: Wilmanns, M.]] | [[Category: Wilmanns, M.]] | ||
| - | [[Category: XMTB, Mycobacterium | + | [[Category: XMTB, Mycobacterium Tuberculosis Structural Proteomics Project.]] |
[[Category: DKA]] | [[Category: DKA]] | ||
[[Category: acyltransferase]] | [[Category: acyltransferase]] | ||
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[[Category: xmtb]] | [[Category: xmtb]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:40:53 2008'' |
Revision as of 13:40, 21 February 2008
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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 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
Page seeded by OCA on Thu Feb 21 15:40:53 2008
Categories: 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
