Crystal structure of the putative HOCl and HOSCN-responsive peroxiredoxin RclX from Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen that often evades eradication by the host immune response, particularly in immunocompromised individuals.Host immune cells produce various antimicrobial oxidants, including H 2 O 2 , HOCl, and HOSCN.Recently, a putative peroxiredoxin, RclX, was identified in P. aeruginosa as a highly upregulated gene in response to HOCl and HOSCN.However, the mechanism by which RclX scavenges HOCl and HOSCN stress remains unclear.In this study, we determined the crystal structure of RclX in homohexameric form.The overall structure of RclX closely resembled that of lpg0406, a carboxymuconolactone decarboxylase (CMD) family member from Legionella pneumophila.We found a hydrogen peroxide molecule near the substrate binding pocket, and the conserved CXXC motifs formed disulfide bond bridges in the crystal structure.Our findings provide structural insights into how P. aeruginosa exhibits high resistance to HOCl and HOSCN during host immune responses, with implications for eradicating persistent P. aeruginosa infections.