2FK8

Crystal structure of Hma (MmaA4) from Mycobacterium tuberculosis complexed with S-adenosylmethionine

2FK8 の概要

• エントリーDOI: 10.2210/pdb2fk8/pdb
• 関連するPDBエントリー: 1KP9 1KPG 1KPH 1KPI 1L1E 1TPY 2FK7
• 分子名称: methoxy mycolic acid synthase 4, S-ADENOSYLMETHIONINE (3 entities in total)
• 機能のキーワード: s-adenosylmethionine-dependent methyltransferase fold, transferase
• 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: 36919.74

構造登録者

Boissier, F.,Guillet, V.,Mourey, L. (登録日: 2006-01-04, 公開日: 2006-01-17, 最終更新日: 2023-08-30)

主引用文献

Boissier, F.,Bardou, F.,Guillet, V.,Uttenweiler-Joseph, S.,Daffe, M.,Quemard, A.,Mourey, L.
Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis.
J.Biol.Chem., 281:4434-4445, 2006

PubMed Abstract: Mycolic acids are major and specific components of the cell envelope of Mycobacteria that include Mycobacterium tuberculosis, the causative agent of tuberculosis. Their metabolism is the target of the most efficient antitubercular drug currently used in therapy, and the enzymes that are involved in the production of mycolic acids represent important targets for the development of new drugs effective against multidrug-resistant strains. Among these are the S-adenosylmethionine-dependent methyltransferases (SAM-MTs) that catalyze the introduction of key chemical modifications in defined positions of mycolic acids. Some of these subtle structural variations are known to be crucial for both the virulence of the tubercle bacillus and the permeability of the mycobacterial cell envelope. We report here the structural characterization of the enzyme Hma (MmaA4), a SAM-MT that is unique in catalyzing the introduction of a methyl branch together with an adjacent hydroxyl group essential for the formation of both keto- and methoxymycolates in M. tuberculosis. Despite the high propensity of Hma to proteolytic degradation, the enzyme was produced and crystallized, and its three-dimensional structure in the apoform and in complex with S-adenosylmethionine was solved to about 2 A. Thestructuresshowtheimportantroleplayedbythemodificationsfound within mycolic acid SAM-MTs, especially thealpha2-alpha3 motif and the chemical environment of the active site. Essential information with respect to cofactor and substrate binding, selectivity and specificity, and about the mechanism of catalytic reaction were derived.

PubMed: 16356931
DOI: 10.1074/jbc.M510250200

実験手法

X-RAY DIFFRACTION (2 Å)