2G5F

The structure of MbtI from Mycobacterium Tuberculosis, the first enzyme in the synthesis of Mycobactin, reveals it to be a salicylate synthase

2G5F の概要

• エントリーDOI: 10.2210/pdb2g5f/pdb
• 分子名称: COG0147: Anthranilate/para-aminobenzoate synthases component I, PYRUVIC ACID, IMIDAZOLE, ... (5 entities in total)
• 機能のキーワード: beta sandwhich, structural genomics, psi, protein structure initiative, tb structural genomics consortium, tbsgc, biosynthetic protein
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 196121.72

構造登録者

Harrison, A.J.,Lott, J.S.,Yu, M.,Ramsay, R.,Baker, E.N.,TB Structural Genomics Consortium (TBSGC) (登録日: 2006-02-22, 公開日: 2006-09-05, 最終更新日: 2023-11-15)

主引用文献

Harrison, A.J.,Gardenborg, T.,Yu, M.,Middleditch, M.,Ramsay, R.J.,Baker, E.N.,Lott, J.S.
The Structure of MbtI from Mycobacterium tuberculosis, the First Enzyme in the Biosynthesis of the Siderophore Mycobactin, Reveals It To Be a Salicylate Synthase
J.Bacteriol., 188:6081-6091, 2006

PubMed Abstract: The ability to acquire iron from the extracellular environment is a key determinant of pathogenicity in mycobacteria. Mycobacterium tuberculosis acquires iron exclusively via the siderophore mycobactin T, the biosynthesis of which depends on the production of salicylate from chorismate. Salicylate production in other bacteria is either a two-step process involving an isochorismate synthase (chorismate isomerase) and a pyruvate lyase, as observed for Pseudomonas aeruginosa, or a single-step conversion catalyzed by a salicylate synthase, as with Yersinia enterocolitica. Here we present the structure of the enzyme MbtI (Rv2386c) from M. tuberculosis, solved by multiwavelength anomalous diffraction at a resolution of 1.8 A, and biochemical evidence that it is the salicylate synthase necessary for mycobactin biosynthesis. The enzyme is critically dependent on Mg2+ for activity and produces salicylate via an isochorismate intermediate. MbtI is structurally similar to salicylate synthase (Irp9) from Y. enterocolitica and the large subunit of anthranilate synthase (TrpE) and shares the overall architecture of other chorismate-utilizing enzymes, such as the related aminodeoxychorismate synthase PabB. Like Irp9, but unlike TrpE or PabB, MbtI is neither regulated by nor structurally stabilized by bound tryptophan. The structure of MbtI is the starting point for the design of inhibitors of siderophore biosynthesis, which may make useful lead compounds for the production of new antituberculosis drugs, given the strong dependence of pathogenesis on iron acquisition in M. tuberculosis.

PubMed: 16923875
DOI: 10.1128/JB.00338-06

実験手法

X-RAY DIFFRACTION (1.8 Å)