8WO3

Crystal structure of H. pylori isoleucyl-tRNA synthetase (HpIleRS) in complex with Mupirocin

Summary for 8WO3

• Entry DOI: 10.2210/pdb8wo3/pdb
• Related: 8WNF
• Descriptor: Isoleucine--tRNA ligase, ZINC ION, GLYCEROL, ... (6 entities in total)
• Functional Keywords: isoleucyl-trna synthetase, helicobacter pylori, hpilers, ilers, aminoacylation, ligase
• Biological source: Helicobacter pylori (Campylobacter pylori)
• Total number of polymer chains: 1
• Total formula weight: 107221.97

Authors

Guo, Y.,Li, S.,Zhang, T. (deposition date: 2023-10-06, release date: 2024-02-14, Last modification date: 2024-03-27)

Primary citation

Chen, X.,Guo, Y.,Shi, J.,Wang, Y.,Guo, X.,Wu, G.,Li, S.,Zhang, T.
Structural basis for substrate and antibiotic recognition by Helicobacter pylori isoleucyl-tRNA synthetase.
Febs Lett., 598:521-536, 2024

PubMed Abstract: 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.

PubMed: 38246751
DOI: 10.1002/1873-3468.14805

Experimental method

X-RAY DIFFRACTION (2.2 Å)