Structural basis for substrate and antibiotic recognition by Helicobacter pylori isoleucyl-tRNA synthetase

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.

Keywords: Helicobacter pylori; aminoacylation site; crystal structure; isoleucyl-tRNA synthetase; mupirocin.

Publication types

  • Letter

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Helicobacter Infections*
  • Helicobacter pylori* / enzymology
  • Humans
  • Isoleucine-tRNA Ligase / chemistry
  • Isoleucine-tRNA Ligase / metabolism
  • Prospective Studies


  • Anti-Bacterial Agents
  • Isoleucine-tRNA Ligase