Structure and function of persulfide dioxygenase from Pseudomonas aeruginosa: Implications on H2S homeostasis and interplay with nitric oxide

Hydrogen sulfide is an important signaling molecule, beneficial at physiological concentrations but harmful at higher levels, due to which a tight control of its bioavailability is essential. Here, we investigated persulfide dioxygenase, an enzyme involved in H2S catabolism, from the pathogen Pseudomonas aeruginosa (PaPDO). Deletion of the gene pdo led to a 4-fold increase in H2S concentration, confirming its physiological role. The recombinant enzyme was structurally characterized at 2.06 Å resolution and assigned to the metallo-β-lactamase superfamily. Compared with its human homolog, PaPDO displayed a different dimerization area and a larger active site, suggesting different substrate preferences. Functionally, PaPDO catalyzed glutathione persulfide dioxygenation with a high turnover rate, and its activity was enhanced by reduced glutathione. Interestingly, the results show that PaPDO binds to nitric oxide, which reversibly inhibits its catalytic activity. These findings reveal a novel mechanism of crosstalk between hydrogen sulfide and nitric oxide signaling and provide insights into redox regulation in a multidrug-resistant pathogen.