Self-S-sulfonation in a bacterial persulfide dioxygenase mediates thiol persulfide detoxification

Le résumé fourni par la source

A ubiquitous class of non-heme Fe(II) enzymes, the persulfide dioxygenases (PDOs), provide protection against hydrogen sulfide (H2S) poisoning. The PDO in humans is a single-domain enzyme, while bacterial PDOs, such as CstB of Staphylococcus aureus, are often fused to a sulfurtransferase (rhodanese) module. Canonical PDOs cleave the S-S bond of glutathione persulfide (GSSH) to produce GSH and sulfite (SO32–). In contrast, CstB, via an unknown mechanism, converts two RSSH to thiosulfate (S2O32–) without the release of sulfite. Six crystallographic structures of S. aureus CstB reveal that a Cys-Gly sequence (C201-G202) in a CstB-unique dynamic loop functions as a glutathione mimic, occupying one face of the hemifacial octahedral Fe(II) coordination site. We establish that CstB self-S-sulfonates C201 in a thiol persulfide, Fe(II) and O2-dependent manner, which is then shuttled to a persulfidated C408 in the rhodanese domain 27 Å away via electrostatic steering to generate thiosulfate as the sole oxidation product. Both C201A and C408A CstBs are inactive in O2-consumption. Self-S-sulfonation ensures rapid clearance of diverse reactive sulfur species under conditions where these species accumulate, permitting S. aureus to harness their cytoprotective effects while avoiding cellular toxicity.

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