Inhibiting adenylate-forming enzymes via a new reaction-hijacking mechanism

该项目旨在鉴定和验证疟疾寄生虫中对反应劫持抑制敏感的腺苷酸形成酶。这类酶可以通过一种新的机制被诱导合成它们自己的核苷氨基磺酸盐抑制剂缀合物。本项目希望为这种新的抑制机制的分子基础和寄生虫中的敏感靶酶提供新的知识。腺苷酸形成酶在蛋白质翻译和脂肪酸代谢等多种生物化学途径中起着关键作用。该项目旨在为未来抗寄生虫药物的设计提供新的范例。

This project aims to identify and validate the adenylate-forming enzymes that are susceptible to reaction-hijacking inhibition in malaria parasites. This class of enzymes can be induced to synthesise their own nucleoside sulfamate inhibitor conjugates via a novel mechanism. This project expects to provide new knowledge about the molecular basis of this novel inhibition mechanism and susceptible target enzymes in the parasites. Adenylate-forming enzymes play critical roles in a diverse range of biochemical pathways, such as protein translation and fatty acid metabolism. The project seeks to deliver a new paradigm for the design of future antiparasitic agents.