3LOG

Crystal structure of MbtI from Mycobacterium tuberculosis

3LOG の概要

• エントリーDOI: 10.2210/pdb3log/pdb
• 分子名称: Isochorismate synthase/isochorismate-pyruvate lyase mbtI, SUCCINIC ACID, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: chorismate, salicylate, anthranilate, isochorismate, isochorismate synthase, isochorismate lyase, ion transport, isomerase, lyase, metal-binding, multifunctional enzyme, transport
• 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: 196442.86

構造登録者

Bulloch, E.M.M.,Lott, J.S.,Baker, E.N.,Johnston, J.M. (登録日: 2010-02-03, 公開日: 2011-02-09, 最終更新日: 2023-11-01)

主引用文献

Manos-Turvey, A.,Bulloch, E.M.,Rutledge, P.J.,Baker, E.N.,Lott, J.S.,Payne, R.J.
Inhibition studies of Mycobacterium tuberculosis salicylate synthase (MbtI).
Chemmedchem, 5:1067-1079, 2010

PubMed Abstract: Mycobacterium tuberculosis salicylate synthase (MbtI), a member of the chorismate-utilizing enzyme family, catalyses the first committed step in the biosynthesis of the siderophore mycobactin T. This complex secondary metabolite is essential for both virulence and survival of M. tuberculosis, the etiological agent of tuberculosis (TB). It is therefore anticipated that inhibitors of this enzyme may serve as TB therapies with a novel mode of action. Herein we describe the first inhibition study of M. tuberculosis MbtI using a library of functionalized benzoate-based inhibitors designed to mimic the substrate (chorismate) and intermediate (isochorismate) of the MbtI-catalyzed reaction. The most potent inhibitors prepared were those designed to mimic the enzyme intermediate, isochorismate. These compounds, based on a 2,3-dihydroxybenzoate scaffold, proved to be low-micromolar inhibitors of MbtI. The most potent inhibitors in this series possessed hydrophobic enol ether side chains at C3 in place of the enol-pyruvyl side chain found in chorismate and isochorismate.

PubMed: 20512795
DOI: 10.1002/cmdc.201000137

実験手法

X-RAY DIFFRACTION (1.73 Å)