Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University, Sixth People's Hospital of Nantong, Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, 500 Yonghe Road, Nantong, China.
Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai, China.
FEBS Lett. 2024 Mar;598(5):521-536. doi: 10.1002/1873-3468.14805. Epub 2024 Jan 21.
Helicobacter pylori infection is a global health concern, affecting over half of the world's population. Acquiring structural information on pharmacological targets is crucial to facilitate inhibitor design. Here, we have determined the crystal structures of H. pylori isoleucyl-tRNA synthetase (HpIleRS) in apo form as well as in complex with various substrates (Ile, Ile-AMP, Val, and Val-AMP) or an inhibitor (mupirocin). Our results provide valuable insights into substrate specificity, recognition, and the mechanism by which HpIleRS is inhibited by an antibiotic. Moreover, we identified Asp641 as a prospective regulatory site and conducted biochemical analyses to investigate its regulatory mechanism. The detailed structural information acquired from this research holds promise for the development of highly selective and effective inhibitors against H. pylori infection.
幽门螺杆菌感染是一个全球性的健康问题，影响了全球超过一半的人口。获得药理学靶点的结构信息对于促进抑制剂设计至关重要。在这里，我们已经确定了幽门螺杆菌异亮氨酰-tRNA 合成酶（HpIleRS）在apo 形式以及与各种底物（Ile、Ile-AMP、Val 和 Val-AMP）或抑制剂（莫匹罗星）复合物的晶体结构。我们的结果提供了有价值的见解，了解底物特异性、识别以及抗生素抑制 HpIleRS 的机制。此外，我们确定了 Asp641 作为一个有前景的调节位点，并进行了生化分析来研究其调节机制。从这项研究中获得的详细结构信息有望开发出针对幽门螺杆菌感染的高度选择性和有效的抑制剂。
