Département de Biochimie, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada.
Wiley Interdiscip Rev RNA. 2011 Mar-Apr;2(2):184-92. doi: 10.1002/wrna.43. Epub 2010 Oct 25.
A number of different human pathogens code for their own enzymes involved in the synthesis of the RNA cap structure. Although the RNA cap structures originating from human and microbial enzymes are often identical, the subunit composition, structure and catalytic mechanisms of the microbial-encoded enzymes involved in the synthesis of the RNA cap structure are often significantly different from those of host cells. As a consequence, these pathogenic cap-forming enzymes are potential targets for antimicrobial drugs. During the past few years, experimental studies have started to demonstrate that inhibition of the RNA capping activity is a reasonable approach for the development of antimicrobial agents. The combination of structural, biochemical, and molecular modeling studies are starting to reveal novel molecules that can serve as starting blocks for the design of more potent and specific antimicrobial agents. Here, we examine various strategies that have been developed to inhibit microbial enzymes involved in the synthesis of the RNA cap structure, emphasizing the challenges remaining to design potent and selective drugs.
许多不同的人类病原体编码其自身参与 RNA 帽结构合成的酶。尽管源自人类和微生物酶的 RNA 帽结构通常是相同的，但参与 RNA 帽结构合成的微生物编码酶的亚基组成、结构和催化机制通常与宿主细胞有很大的不同。因此，这些致病的帽形成酶是潜在的抗菌药物靶标。在过去的几年中，实验研究已开始证明抑制 RNA 加帽活性是开发抗菌药物的合理方法。结构、生化和分子建模研究的结合开始揭示出可作为设计更有效和更具特异性的抗菌药物的起始分子。在这里，我们检查了已开发出的各种抑制参与 RNA 帽结构合成的微生物酶的策略，强调了在设计有效和选择性药物方面仍然存在的挑战。
