2VKL

X-ray crystal structure of the intracellular Chorismate mutase from Mycobactrerium Tuberculosis in complex with malate

2VKL の概要

• エントリーDOI: 10.2210/pdb2vkl/pdb
• 分子名称: RV0948C/MT0975, D-MALATE (3 entities in total)
• 機能のキーワード: helical, tuberculosis, intracellular, chorismate mutase, isomerase
• 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: 10241.90

構造登録者

Okvist, M.,Roderer, K.,Sasso, S.,Kast, P.,Krengel, U. (登録日: 2007-12-20, 公開日: 2008-01-15, 最終更新日: 2024-05-08)

主引用文献

Sasso, S.,Okvist, M.,Roderer, K.,Gamper, M.,Codoni, G.,Krengel, U.,Kast, P.
Structure and Function of a Complex between Chorismate Mutase and Dahp Synthase: Efficiency Boost for the Junior Partner.
Embo J., 28:2128-, 2009

PubMed Abstract: Chorismate mutase catalyzes a key step in the shikimate biosynthetic pathway towards phenylalanine and tyrosine. Curiously, the intracellular chorismate mutase of Mycobacterium tuberculosis (MtCM; Rv0948c) has poor activity and lacks prominent active-site residues. However, its catalytic efficiency increases >100-fold on addition of DAHP synthase (MtDS; Rv2178c), another shikimate-pathway enzyme. The 2.35 A crystal structure of the MtCM-MtDS complex bound to a transition-state analogue shows a central core formed by four MtDS subunits sandwiched between two MtCM dimers. Structural comparisons imply catalytic activation to be a consequence of the repositioning of MtCM active-site residues on binding to MtDS. The mutagenesis of the C-terminal extrusion of MtCM establishes conserved residues as part of the activation machinery. The chorismate-mutase activity of the complex, but not of MtCM alone, is inhibited synergistically by phenylalanine and tyrosine. The complex formation thus endows the shikimate pathway of M. tuberculosis with an important regulatory feature. Experimental evidence suggests that such non-covalent enzyme complexes comprising an AroQ(delta) subclass chorismate mutase like MtCM are abundant in the bacterial order Actinomycetales.

PubMed: 19556970
DOI: 10.1038/EMBOJ.2009.165

実験手法

X-RAY DIFFRACTION (1.65 Å)