Gibbs Morgan E, Lountos George T, Gumpena Rajesh, Waugh David S
Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Acta Crystallogr F Struct Biol Commun. 2019 Sep 1;75(Pt 9):608-615. doi: 10.1107/S2053230X19011154. Epub 2019 Aug 28.
Yersinia pestis, the causative agent of bubonic plague, is one of the most lethal pathogens in recorded human history. Today, the concern is the possible misuse of Y. pestis as an agent in bioweapons and bioterrorism. Current therapies for the treatment of plague include the use of a small number of antibiotics, but clinical cases of antibiotic resistance have been reported in some areas of the world. Therefore, the discovery of new drugs is required to combat potential Y. pestis infection. Here, the crystal structure of the Y. pestis UDP-glucose pyrophosphorylase (UGP), a metabolic enzyme implicated in the survival of Y. pestis in mouse macrophages, is described at 2.17 Å resolution. The structure provides a foundation that may enable the rational design of inhibitors and open new avenues for the development of antiplague therapeutics.
鼠疫耶尔森菌是腺鼠疫的病原体，是人类历史记载中最致命的病原体之一。如今，人们担心鼠疫耶尔森菌可能被滥用作生物武器和生物恐怖主义的制剂。目前治疗鼠疫的方法包括使用少数几种抗生素，但世界上一些地区已报告了抗生素耐药的临床病例。因此，需要发现新药来对抗潜在的鼠疫耶尔森菌感染。在此，以2.17 Å的分辨率描述了鼠疫耶尔森菌UDP-葡萄糖焦磷酸化酶（UGP）的晶体结构，该代谢酶与鼠疫耶尔森菌在小鼠巨噬细胞中的存活有关。该结构为合理设计抑制剂提供了基础，并为抗鼠疫治疗药物的开发开辟了新途径。
