泛酸激酶及其抑制剂的研究进展

Pantothenate Kinase and Its Inhibitors:Current Research Status

辅酶A的生物合成对于病原微生物的生存及致病性至关重要,而作为辅酶A生物合成途径的限速酶——泛酸激酶控制着辅酶A生物合成的起始步骤,且其普遍存在于病原体,并与人体中的同源蛋白相似度极低,故引起人们广泛兴趣,成为潜在的新型抗菌靶标研究的热点,其小分子抑制剂有望开发成为具高选择性、低毒副作用的抗菌药。综述泛酸激酶的分类、特性、晶体结构特征及其调控和成为潜在抗菌药物靶标的可行性,并概述具不同结构类型和抗病原微生物活性的在研泛酸激酶抑制剂。

The biosynthesis of coenzyme A（CoA） plays a vital role in the survival and virulence of pathogenic microorganism. Pantothenate kinase as the rate-limiting enzyme controls the starting step in CoA biosynthesis,which is widespread in the pathogen and of which the similarity to homologous proteins in human is extremely low. Therefore,the kinase has gained much of people＇s interest and has become a hot spot of research for potential new type of antibacterial targets. Its small molecule inhibitors are expected to be developed into the antimicrobials with high selectivity and low toxicity. The classifi cation,property and crystal structure of pantothenate kinase and its regulation as well as the feasibility of its use as a potential antibacterial target were reviewed. The pantothenic acid kinase inhibitors in development with different structures and activities against pathogenic microorganism were summarized.