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

TL;DR

This study explores an enzyme in Pseudomonas aeruginosa that breaks down hydrogen sulfide and interacts with nitric oxide, revealing new insights into how these signaling molecules work together.

Contribution

The paper identifies a novel crosstalk mechanism between hydrogen sulfide and nitric oxide signaling via PaPDO in a multidrug-resistant pathogen.

Findings

Deletion of the pdo gene in Pseudomonas aeruginosa increases hydrogen sulfide concentration fourfold.

PaPDO binds to nitric oxide, which reversibly inhibits its catalytic activity.

PaPDO has a distinct dimerization area and larger active site compared to its human homolog.

Abstract

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.

•PaPDO 3D structure displays the typical metallo-β-lactamase fold with a dimeric organization•Deletion of the gene pdo leads to a 4-fold increase in hydrogen sulfide concentration•PaPDO catalyzes glutathione persulfide dioxygenation with a high turnover rate•Nitric oxide binds to PaPDO, potently and reversibly inhibiting its activity

PaPDO 3D structure displays the typical metallo-β-lactamase fold with a dimeric organization

Deletion of the gene pdo leads to a 4-fold increase in hydrogen sulfide concentration

PaPDO catalyzes glutathione persulfide dioxygenation with a high turnover rate

Nitric oxide binds to PaPDO, potently and reversibly inhibiting its activity

Biochemistry; Microbiology; Structural biology

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