靶向变异链球菌谷氨酸消旋酶的研究进展

Research progress on the targeting of glutamate racemase of Streptococcus mutans

变异链球菌是龋病发生的始动因子,与人类龋病密切相关。抑制变异链球菌致龋毒力相关的基因和酶,可影响细菌毒力因子的产生,降低细菌的致龋能力,有助于龋病的预防和治疗。谷氨酸消旋酶是一类不需辅助因子,专一催化L型和D型谷氨酸之间相互转化的酶,为细胞壁肽聚糖合成提供D-谷氨酸,是细菌生长的关键酶,目前已经成为研究和开发新型抗菌药物的新靶标。特异性靶向变异链球菌谷氨酸消旋酶,有望为龋病防治提供新的思路和方法。本文对谷氨酸消旋酶的分类、结构特征、酶抑制剂及基因遗传学等研究进展进行系统阐述,为进一步研究谷氨酸消旋酶与变异链球菌致龋毒力的关系,研发抗龋药物候选靶标提供理论基础。

Streptococcus mutans（S.mutans）is widely considered to be the major etiological factor responsible for dental caries in humans. Strategies selectively inhibiting the specific virulence factors associated with its cariogenicity are promising. Glutamate racemase （MurI） is a cofactor？independent enzyme that catalyzes the interconversion of L？glutamate to D？glutamate,one of the essential amino acids present in the peptidoglycan. As the indispensable enzyme in peptidoglycan biosynthesis,MurI has therefore been an attractive target for therapeutic interventions. In this review,the classifications, structures, inhibitors and genetic studies of MurI are systematically summarized. A comprehensive understanding of the relationship between MurI and cariogenic virulence of S.mutans can provide an important theoretical basis for potential therapeutic applications of dental caries.