Distinct quaternary reaction behavior and stable charge-transfer complex formation in Schistosoma mansoni...

Adults of Schistosoma mansoni reside in the mesenteric veins, where they are naturally exposed to high levels of hydrogen sulfide (H₂S). S. mansoni and other intestinal parasites have adapted to this sulfide-rich environment, but the evolved mechanisms to metabolize sulfide remain unelucidated. Here we reveal that the putative sulfide:quinone oxidoreductase (SQOR) encoded by S. mansoni is indeed an SQOR, catalyzing the first step of sulfide metabolism. We demonstrated that S. mansoni SQOR (SmSQOR) is expressed in eggs, cercaria and adult stages and localized in the mitochondria. The reaction catalyzed by SmSQOR was investigated using sulfane sulfur probe 4 (SSP4) and shown to require the co-presence of sulfide, quinone, and a sulfur acceptor, indicating a quaternary complex-mediated mechanism. Unlike human and bacterial SQORs, purified SmSQOR could not reduce quinones in the presence of sulfide alone unless sulfite, cyanide, or L-cysteine (but not coenzyme A or glutathione) was provided as the sulfur acceptor. In the presence of these sulfur acceptors, SmSQOR formed a long-lived charge-transfer (CT) complex, a transient electronically coupled association between electron donor and acceptor, as indicated by a broad band around 637-755 nm in the spectrum, which was associated with a partial loss of enzyme activity. Moreover, residues critical for CT complex formation and SQOR catalysis were identified. Using SSP4, we also demonstrated that SQOR was active in S. mansoni adult, egg, and cercaria stages. Taken together, these features suggest that metabolism of sulfide proceeds differently in S. mansoni than in humans.