抗菌药物治疗疾病的新靶位--丙氨酸消旋酶  

New Targets for Antibacterial Agent——Alanine Racemase

作　　者：刘晓琴[1] 石亚伟[1] 

机构地区：[1]山西大学生物技术研究所,教育部化学生物学与分子工程重点实验室,太原030006

出　　处：《中国生物化学与分子生物学报》2010年第2期104-108,共5页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金(No.30400065);山西省自然科学基金(No.2007021033);教育部重点项目(No.208020)基金资助~~

摘　　要：丙氨酸消旋酶是以磷酸吡哆醛为辅酶,催化L-丙氨酸与D-丙氨酸相互转化的一种酶,它广泛分布在低等生物,而不存在于人类等高等真核生物中.来自不同物种的丙氨酸消旋酶一级结构同源性较高,其大多功能单位为同源二聚体,拥有2个相同的活性中心,每个活性中心均是由来自不同亚基的2个保守残基共同组成.丙氨酸消旋酶催化生成的产物D-丙氨酸是合成细菌细胞壁肽聚糖的重要成分,也是调节细菌孢子萌芽的关键因子.因而丙氨酸消旋酶与由细菌引起的肺结核、炭疽热、中耳炎等疾病密切相关.近年来丙氨酸消旋酶已成为设计抗菌药物的又一理想靶位.本文从丙氨酸消旋酶的结构、功能、作用机理、抑制剂以及其与疾病的关系等方面进行了阐述.Alanine racemase（AlaR） is a pyridoxal 5＇-phosphate（PLP）-dependent enzyme that catalyzes the interconversion of L-and D-alanine isomers.AlaR belong to the fold-type Ⅲ group of PLP-dependent enzymes.It is ubiquitously existed and highly conserved in bacteria,but is generally absent in human and higher eukaryotes.The AlaR functioned mostly as homodimers comprised of two identical catalytic active sites which contained two conserved residues each from different monomers.AlaR plays an important role in the bacterial growth to provide D-alanine,a key molecule in the peptidyl-glycan assembly and crosslinking and an essential factor to modulate bacterial spore germination.AlaR is also associated with human diseases,such as tuberculosis,anthrax,and otitis,therefore can be regarded as an potential target for the design of new antibacterial drugs.In this review,the recent advances in alanine racemases tudies with the aspects of structure,function,mechanism,and inhibitors will be discussed.

关 键 词：丙氨酸消旋酶 结构 作用机理 功能 疾病 

分 类 号：Q936[生物学—微生物学]