PDF(Pubmed)
Abstract：
Multiple drug resistance is the main obstacle in the treatment of bacterial diseases. Resistance against antibiotics demands the exploration of new antimicrobial drug targets. A variety of in silico and genetic approaches show that the enzymes of the riboflavin biosynthetic pathway are crucial for the survival of bacteria. This pathway is absent in humans thus enzymes of the riboflavin biosynthetic pathway are emerging drug targets for resistant pathogenic bacterial strains. Exploring the structural details, their mechanism of action, intermediate elucidation, and interaction analysis would help in designing suitable inhibitors of these enzymes. The riboflavin biosynthetic pathway consists of seven distinct enzymes, namely, 3,4-dihydroxy-2-butanone 4-phosphate synthase, GTP cyclohydrolase II, pyrimidine deaminase/reductase, phosphatase, lumazine synthase, and riboflavin synthase. The present review summarizes the research work that has been carried out on these enzymes in terms of their structures, active site architectures, and molecular mechanism of catalysis. This review also walks through small molecule inhibitors that have been developed against several of these enzymes.
摘要：
多重耐药是治疗细菌性疾病的主要障碍。对抗生素的耐药性需要探索新的抗菌药物靶标。各种计算机模拟和遗传方法表明，核黄素生物合成途径的酶对于细菌的生存至关重要。该途径在人类中不存在，因此核黄素生物合成途径的酶是耐药致病性细菌菌株的新兴药物靶标。探索结构细节，他们的作用机制，中间阐明，和相互作用分析将有助于设计这些酶的合适抑制剂。核黄素生物合成途径由七种不同的酶组成，即,3,4-二羟基-2-丁酮4-磷酸合成酶,GTP环化水解酶II,嘧啶脱氨酶/还原酶，磷酸酶lumazine合酶,和核黄素合成酶.本综述总结了在这些酶的结构方面已经进行的研究工作，活动站点体系结构，和催化的分子机理。这篇综述还介绍了针对这些酶中的几种开发的小分子抑制剂。
