4fx9 | pdb_00004fx9
Structure of the Pyrococcus horikoshii CoA persulfide/polysulfide reductase
Structural highlights
FunctionNCPPR_PYRHO Catalyzes the NAD(P)H-dependent reduction of polysulfide, CoA-polysulfides, and CoA persulfide, as well as the reduction of a range of other small persulfides, including TNB and glutathione persulfides. The likely in vivo substrates are di-, poly-, and persulfide derivatives of coenzyme A, although polysulfide itself is also efficiently reduced (PubMed:23530771). Shows coenzyme A disulfide reductase (CoADR) activity with both NADH and NADPH, with a preference for NADPH (PubMed:15720393). May also play a role in the reduction of elemental sulfur (PubMed:23530771).[1] [2] Publication Abstract from PubMedFAD and NAD(P)H-dependent coenzyme A disulfide reductases/poly-sulfide reductases (CoADR/Psr) have been proposed to be important for the reduction of sulfur and disulfides in the sulfur-reducing anaerobic hyperthermophiles Pyrococcus horikoshii and Pyrococcus furiosus, however, the form(s) of sulfur that the enzyme actually reduces are not clear. Here we determined the structure for the FAD- and coenzyme A-containing holoenzyme from P. horikoshii to 2.7 A resolution and characterized its substrate specificity. The enzyme is relatively promiscuous, and reduces a range of disulfide, persulfide and polysulfide compounds. These results indicate that the likely in vivo substrates are NAD(P)H and di, poly and persulfide derivatives of coenzyme A, although polysulfide itself is also efficiently reduced. The role of the enzyme in the reduction of elemental sulfur (S8) in situ is not, however, ruled out by these results, and the possible roles of this substrate are discussed. During aerobic persulfide reduction, rapid recycling of the persulfide substrate was observed, which is proposed to occur via sulfide oxidation by O2 and/or H2O2. As expected, this reaction disappears under anaerobic conditions and may explain observations by others that CoADR is not essential for S0respiration in Pyrococcus or Thermococcus but appears to participate in oxidative defense in the presence of S0. When compared to the homologous Npsr enzyme from Shewanella loihica PV-4 and homologous enzymes known to reduce CoA disulfide, the phCoADR structure shows a relatively restricted substrate channel leading into the sulfur-reducing side of the FAD isoalloxazine ring, suggesting how this enzyme class may select for specific disulfide substrates. Characterization of the structure and substrate specificity of the pyrococcal CoADR/Psr: Implications for S0-based respiration and a sulfur-dependent antioxidant system in Pyrococcus.,Herwald S, Liu AY, Zhu BE, Sea KW, Lopez KM, Sazinsky MH, Crane Iii EJ Biochemistry. 2013 Mar 26. PMID:23530771[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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