NSR_PYRFU
ID NSR_PYRFU Reviewed; 442 AA.
AC Q8U1M0;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=NAD(P)H sulfur oxidoreductase (CoA-dependent) {ECO:0000305};
DE Short=NSR {ECO:0000303|PubMed:17449625};
DE EC=1.8.1.18 {ECO:0000269|PubMed:17449625};
DE AltName: Full=Coenzyme A disulfide reductase {ECO:0000303|PubMed:15720393};
DE Short=CoA-disulfide reductase {ECO:0000305};
DE Short=CoADR {ECO:0000303|PubMed:15720393};
DE EC=1.8.1.14 {ECO:0000269|PubMed:15720393};
DE AltName: Full=NAD(P)H oxidase {ECO:0000305};
DE Short=NOX {ECO:0000303|PubMed:24723088};
DE EC=1.6.3.- {ECO:0000269|PubMed:24723088};
GN Name=nsr {ECO:0000303|PubMed:21965560}; OrderedLocusNames=PF1186;
OS Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1).
OC Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC Pyrococcus.
OX NCBI_TaxID=186497;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43587 / DSM 3638 / JCM 8422 / Vc1;
RX PubMed=10430560; DOI=10.1093/genetics/152.4.1299;
RA Maeder D.L., Weiss R.B., Dunn D.M., Cherry J.L., Gonzalez J.M.,
RA DiRuggiero J., Robb F.T.;
RT "Divergence of the hyperthermophilic archaea Pyrococcus furiosus and P.
RT horikoshii inferred from complete genomic sequences.";
RL Genetics 152:1299-1305(1999).
RN [2]
RP FUNCTION AS A COA-DISULFIDE REDUCTASE, AND CATALYTIC ACTIVITY.
RX PubMed=15720393; DOI=10.1111/j.1742-4658.2005.04555.x;
RA Harris D.R., Ward D.E., Feasel J.M., Lancaster K.M., Murphy R.D.,
RA Mallet T.C., Crane E.J. III;
RT "Discovery and characterization of a coenzyme A disulfide reductase from
RT Pyrococcus horikoshii. Implications for this disulfide metabolism of
RT anaerobic hyperthermophiles.";
RL FEBS J. 272:1189-1200(2005).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBUNIT, SUBCELLULAR LOCATION, AND INDUCTION.
RC STRAIN=ATCC 43587 / DSM 3638 / JCM 8422 / Vc1;
RX PubMed=17449625; DOI=10.1128/jb.00031-07;
RA Schut G.J., Bridger S.L., Adams M.W.;
RT "Insights into the metabolism of elemental sulfur by the hyperthermophilic
RT archaeon Pyrococcus furiosus: characterization of a coenzyme A-dependent
RT NAD(P)H sulfur oxidoreductase.";
RL J. Bacteriol. 189:4431-4441(2007).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21965560; DOI=10.1128/jb.05445-11;
RA Bridger S.L., Clarkson S.M., Stirrett K., DeBarry M.B., Lipscomb G.L.,
RA Schut G.J., Westpheling J., Scott R.A., Adams M.W.;
RT "Deletion strains reveal metabolic roles for key elemental sulfur-
RT responsive proteins in Pyrococcus furiosus.";
RL J. Bacteriol. 193:6498-6504(2011).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND SUBUNIT.
RX PubMed=24723088; DOI=10.1007/s00792-014-0643-z;
RA Harnvoravongchai P., Kobori H., Orita I., Nakamura S., Imanaka T.,
RA Fukui T.;
RT "Characterization and gene deletion analysis of four homologues of group 3
RT pyridine nucleotide disulfide oxidoreductases from Thermococcus
RT kodakarensis.";
RL Extremophiles 18:603-616(2014).
CC -!- FUNCTION: Catalyzes the CoA-dependent reduction of elemental sulfur
CC (S(0)) to produce hydrogen sulfide (PubMed:17449625, PubMed:24723088).
CC Can use both NADPH and NADH, but shows a preference for NADPH
CC (PubMed:24723088). May enable S(0) to be used, via sulfide, for iron-
CC sulfur cluster synthesis by SipA (Probable). Also shows coenzyme A
CC disulfide reductase (CoADR) activity with both NADH and NADPH
CC (PubMed:15720393, PubMed:17449625). However, CoADR specific activity is
CC about 20-fold lower than the sulfur reduction assay and CoADR activity
CC appears to be an artifactual side reaction and is not thought to have
CC any physiological relevance (PubMed:17449625). Also shows NAD(P)H
CC oxidase activity with both NADH and NADPH (PubMed:24723088).
CC {ECO:0000269|PubMed:15720393, ECO:0000269|PubMed:17449625,
CC ECO:0000269|PubMed:24723088, ECO:0000305|PubMed:21965560}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hydrogen sulfide + NADP(+) = NADPH + sulfur;
CC Xref=Rhea:RHEA:36595, ChEBI:CHEBI:26833, ChEBI:CHEBI:29919,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.8.1.18;
CC Evidence={ECO:0000269|PubMed:17449625, ECO:0000269|PubMed:24723088};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:36597;
CC Evidence={ECO:0000269|PubMed:17449625, ECO:0000269|PubMed:24723088};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hydrogen sulfide + NAD(+) = NADH + sulfur;
CC Xref=Rhea:RHEA:36599, ChEBI:CHEBI:26833, ChEBI:CHEBI:29919,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.8.1.18;
CC Evidence={ECO:0000269|PubMed:17449625, ECO:0000269|PubMed:24723088};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:36601;
CC Evidence={ECO:0000269|PubMed:17449625, ECO:0000269|PubMed:24723088};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 CoA + NADP(+) = CoA-disulfide + H(+) + NADPH;
CC Xref=Rhea:RHEA:14705, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:62209; EC=1.8.1.14;
CC Evidence={ECO:0000269|PubMed:15720393, ECO:0000269|PubMed:17449625};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 CoA + NAD(+) = CoA-disulfide + H(+) + NADH;
CC Xref=Rhea:RHEA:14701, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62209;
CC Evidence={ECO:0000269|PubMed:15720393};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:17449625, ECO:0000269|PubMed:24723088};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:O58308};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.5 mM for NADPH {ECO:0000269|PubMed:17449625};
CC KM=3.3 mM for NADH {ECO:0000269|PubMed:17449625};
CC KM=18 uM for CoA {ECO:0000269|PubMed:17449625};
CC KM=10 uM for CoA-disulfide {ECO:0000269|PubMed:17449625};
CC pH dependence:
CC Optimum pH is 6.5 for sulfide production.
CC {ECO:0000269|PubMed:17449625};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17449625,
CC ECO:0000269|PubMed:24723088}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17449625}.
CC -!- INDUCTION: Up-regulated up to sevenfold by elemental sulfur addition.
CC {ECO:0000269|PubMed:17449625}.
CC -!- DISRUPTION PHENOTYPE: Deletion mutant does not exhibit an obvious
CC phenotype and produces sulfide and acetate in amounts comparable to
CC those produced by the parent strain. {ECO:0000269|PubMed:21965560}.
CC -!- SIMILARITY: Belongs to the class-III pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AE009950; AAL81310.1; -; Genomic_DNA.
DR RefSeq; WP_011012327.1; NZ_CP023154.1.
DR AlphaFoldDB; Q8U1M0; -.
DR SMR; Q8U1M0; -.
DR STRING; 186497.PF1186; -.
DR PRIDE; Q8U1M0; -.
DR EnsemblBacteria; AAL81310; AAL81310; PF1186.
DR GeneID; 41712995; -.
DR KEGG; pfu:PF1186; -.
DR PATRIC; fig|186497.12.peg.1247; -.
DR eggNOG; arCOG01069; Archaea.
DR HOGENOM; CLU_003291_1_3_2; -.
DR OMA; WVSHAPC; -.
DR OrthoDB; 40511at2157; -.
DR PhylomeDB; Q8U1M0; -.
DR BioCyc; MetaCyc:MON-18049; -.
DR BRENDA; 1.8.1.18; 5243.
DR Proteomes; UP000001013; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0050451; F:CoA-disulfide reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0043914; F:NADPH:sulfur oxidoreductase activity; IEA:UniProtKB-EC.
DR GO; GO:0003756; F:protein disulfide isomerase activity; IEA:InterPro.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR Gene3D; 3.50.50.60; -; 3.
DR InterPro; IPR017758; CoA_disulphide_reductase.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer_sf.
DR InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR Pfam; PF02852; Pyr_redox_dim; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF55424; SSF55424; 1.
DR TIGRFAMs; TIGR03385; CoA_CoA_reduc; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; FAD; Flavoprotein; NAD; NADP; Oxidoreductase;
KW Redox-active center; Reference proteome.
FT CHAIN 1..442
FT /note="NAD(P)H sulfur oxidoreductase (CoA-dependent)"
FT /id="PRO_0000184698"
FT ACT_SITE 45
FT /note="Redox-active"
FT /evidence="ECO:0000250|UniProtKB:O58308"
FT BINDING 13..14
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O58308"
FT BINDING 24
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:O58308"
FT BINDING 35..36
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O58308"
FT BINDING 41..45
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:O58308"
FT BINDING 42..44
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O58308"
FT BINDING 62..63
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:O58308"
FT BINDING 72
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:O58308"
FT BINDING 82
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O58308"
FT BINDING 280
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O58308"
FT BINDING 298
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O58308"
FT BINDING 302
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:O58308"
FT BINDING 358
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:O58308"
FT BINDING 422
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O58308"
FT BINDING 430
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:O58308"
FT BINDING 438
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:O58308"
SQ SEQUENCE 442 AA; 48720 MW; 2329E5F596F1CA6A CRC64;
MEKKKVVIIG GGAAGMSAAS RVKRLRPEWD VKVFEATEWV SHAPCGIPYV VEGIAPKEKL
MHYPPEVFIK KRGIDLHLKA EVIEVETGYV RVRENGEEKS YEWDYLVFAN GASPQIPEIE
GVDLPGVFTA DLPPDAVAIT EYMEKNKVED VVIIGTGYIA LEMAEAFVTR GKNVTLIGRS
ERVLRKTFDK EITDIVEEKL RQHLNLRLHE KTLSIEGRER VEKVITDGGE YKADLVIIAT
GIKPNVELAK QLGVKIGETG AIWTNEKMQT SVENVYAAGD VAETKHVITG KRVWIPLAPA
GNKMGYVAGS NIAGKEIEFP GVLGTSITKF MDLEIGKTGL TENEAVKEGY DVRTAFIKAN
TKPHYYPGGR EIWLKGVVDN ETNRLLGVQA VGAEILPRID SAAAMITAGF TTKDVFFTDL
AYAPPFAPVW DPLIVLARVL KF
