Title:Investigation of Potential Inhibitors of Chorismate-Utilizing Enzymes
Volume: 22
Issue: 11
Author(s): Marketa Svarcova, Martin Kratky and Jarmila Vinsova
Affiliation:
关键词:
邻氨基苯甲酸盐合成酶，抗菌剂，支酸变位酶
摘要: Chorismate-utilizing enzymes (CUE) such as chorismate mutase, anthranilate synthase,
chorismate pyruvate-lyase, 4-amino-4-deoxychorismate synthase, isochorismate synthase and salicylate
synthase are responsible for converting chorismate into various products necessary for the survival
of bacteria. The absence of these enzymes in humans and their importance in the virulence and survival
of bacteria make them suitable targets for potential antimicrobial compounds. Furthermore, the
CUE have significant structural homology and similar catalytic mechanisms, enabling the strategy of
affecting multiple enzymes with one single inhibitor. This review follows up the investigation of
mechanisms of CUE-catalysed reactions and the concurrent development of CUE inhibitors. Many active compounds
were found amongst the structures mimicking the transition state of chorismate during the reaction. Most recently, high
nanomolar and low micromolar inhibitors against isochorismate-pyruvate lyase were identified, which were also effective
against chorismate mutase and salicylate synthase and belong to the most active inhibitors reported up to date.
