1W66

Structure of a lipoate-protein ligase b from Mycobacterium tuberculosis

1W66 の概要

• エントリーDOI: 10.2210/pdb1w66/pdb
• 分子名称: LIPOYLTRANSFERASE, DECANOIC ACID (3 entities in total)
• 機能のキーワード: lipoate-protein ligase b, lipoyltransferase, lipoic acid, acyltransferase, transferase, mycobacterium tuberculosis structural proteomics project, xmtb, structural genomics
• 由来する生物種: MYCOBACTERIUM TUBERCULOSIS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24510.04

構造登録者

Ma, Q.,Wilmanns, M. (登録日: 2004-08-13, 公開日: 2005-12-08, 最終更新日: 2024-11-13)

主引用文献

Ma, Q.,Zhao, X.,Eddine, A.N.,Geerlof, A.,Li, X.,Cronan, J.E.,Kaufmann, S.H.,Wilmanns, M.
The Mycobacterium Tuberculosis Lipb Enzyme Functions as a Cysteine/Lysine Dyad Acyltransferase.
Proc.Natl.Acad.Sci.USA, 103:8662-, 2006

PubMed Abstract: 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.

PubMed: 16735476
DOI: 10.1073/PNAS.0510436103

実験手法

X-RAY DIFFRACTION (1.08 Å)