二氢乳清酸脱氢酶的结构特征和催化循环研究进展

Structural characteristics and catalytic cycle of dihydroorotate dehydrogenase-a review

二氢乳清酸脱氢酶是黄素依赖的线粒体酶,它催化嘧啶从头合成的第4步反应,将二氢乳清酸氧化为乳清酸。通过选择性抑制二氢乳清酸脱氢酶,从而抑制嘧啶的合成,已被开发用于治疗癌症、自身免疫性疾病、细菌或病毒感染以及寄生虫疾病等。抑制剂的开发需详细了解二氢乳清酸脱氢酶的结构特征和催化循环机制。因此,文中主要从这两个方面进行了综述,并展望了该酶的抑制剂在临床应用中的前景。

Dihydroorotate dehydrogenase is a flavin-dependent mitochondrial enzyme to catalyze the fourth step of the de novo synthesis of pyrimidine and to oxidize dihydroorotate to orotate.By selectively inhibiting dihydroorotate dehydrogenase,thereby inhibiting pyrimidine synthesis,the enzyme has been developed for the treatment of cancer,autoimmune diseases,bacterial or viral infections,parasitic diseases and so on.The development of inhibitory drugs requires a detailed understanding of the structural characteristics and catalytic cycle mechanism of dihydroorotate dehydrogenase.Therefore,this paper reviews these two aspects,and indicates perspectives of these inhibitors in clinical application.