摘要
分支酸利用酶(CUE),如分支酸变位酶、邻氨基苯甲酸盐合成酶、分支酸丙酮酸盐裂解酶、4-氨基-4-脱氧分支酸合成酶、异分支酸合成酶和水杨酸合酶是分支酸转化为细菌的生存所必需的各种产品的主要来源。在人体中,这些酶的缺失危害以及它们在细菌生存和发挥毒力时的重要性,让它们成为合适的抗菌化合物的潜在靶标。此外,CUE有显著的结构相似性和类似的催化机制,一种抑制剂可影响多个酶。本文遵循CUE催化反应机制的调查研究和抑制剂的研发进展。发现许多与分支酸反应过渡状态的相似结构的活性物质。最近,高微摩尔和低微摩尔的抑制剂对异分支酸-丙酮酸盐裂合酶被确定,它们能有效对抗分支酸变位酶和水杨酸合成酶,且属于具有最好活性的抑制剂的最新报道。
关键词: 邻氨基苯甲酸盐合成酶,抗菌剂,支酸变位酶
Current Medicinal Chemistry
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.
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Marketa Svarcova, Martin Kratky and Jarmila Vinsova , Investigation of Potential Inhibitors of Chorismate-Utilizing Enzymes, Current Medicinal Chemistry 2015; 22 (11) . https://dx.doi.org/10.2174/0929867322666150209152446
DOI https://dx.doi.org/10.2174/0929867322666150209152446 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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