NCPPR_PYRHO
ID NCPPR_PYRHO Reviewed; 445 AA.
AC O58308;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=NAD(P)H coenzyme A polysulfide/persulfide reductase {ECO:0000305};
DE EC=1.8.1.- {ECO:0000269|PubMed:23530771};
DE AltName: Full=Coenzyme A disulfide reductase {ECO:0000303|PubMed:15720393, ECO:0000303|PubMed:23530771};
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=Polysulfide reductase {ECO:0000303|PubMed:23530771};
GN OrderedLocusNames=PH0572;
OS Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC
OS 100139 / OT-3).
OC Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC Pyrococcus.
OX NCBI_TaxID=70601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3;
RX PubMed=9679194; DOI=10.1093/dnares/5.2.55;
RA Kawarabayasi Y., Sawada M., Horikawa H., Haikawa Y., Hino Y., Yamamoto S.,
RA Sekine M., Baba S., Kosugi H., Hosoyama A., Nagai Y., Sakai M., Ogura K.,
RA Otsuka R., Nakazawa H., Takamiya M., Ohfuku Y., Funahashi T., Tanaka T.,
RA Kudoh Y., Yamazaki J., Kushida N., Oguchi A., Aoki K., Yoshizawa T.,
RA Nakamura Y., Robb F.T., Horikoshi K., Masuchi Y., Shizuya H., Kikuchi H.;
RT "Complete sequence and gene organization of the genome of a hyper-
RT thermophilic archaebacterium, Pyrococcus horikoshii OT3.";
RL DNA Res. 5:55-76(1998).
RN [2]
RP FUNCTION AS A COA-DISULFIDE REDUCTASE, CATALYTIC ACTIVITY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
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] {ECO:0007744|PDB:3KD9}
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 7-444.
RA Agarwal R., Burley S.K., Swaminathan S.;
RT "Crystal structure of pyridine nucleotide disulfide oxidoreductase from
RT Pyrococcus horikoshii.";
RL Submitted (OCT-2009) to the PDB data bank.
RN [4] {ECO:0007744|PDB:4FX9}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) IN COMPLEX WITH COENZYME A AND FAD,
RP FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND DOMAIN.
RX PubMed=23530771; DOI=10.1021/bi3014399;
RA Herwald S., Liu A.Y., Zhu B.E., Sea K.W., Lopez K.M., Sazinsky M.H.,
RA Crane E.J.;
RT "Structure and substrate specificity of the pyrococcal coenzyme A disulfide
RT reductases/polysulfide reductases (CoADR/Psr): implications for S(0)-based
RT respiration and a sulfur-dependent antioxidant system in Pyrococcus.";
RL Biochemistry 52:2764-2773(2013).
RN [5] {ECO:0007744|PDB:5L1N}
RP X-RAY CRYSTALLOGRAPHY (3.60 ANGSTROMS) OF QUADRUPLE MUTANT IN COMPLEX WITH
RP COENZYME A AND FAD, AND DOMAIN.
RX PubMed=29988575; DOI=10.1002/2211-5463.12439;
RA Sea K., Lee J., To D., Chen B., Sazinsky M.H., Crane E.J.;
RT "A broader active site in Pyrococcus horikoshii CoA disulfide reductase
RT accommodates larger substrates and reveals evidence of subunit asymmetry.";
RL FEBS Open Bio 8:1083-1092(2018).
CC -!- FUNCTION: Catalyzes the NAD(P)H-dependent reduction of polysulfide,
CC CoA-polysulfides, and CoA persulfide, as well as the reduction of a
CC range of other small persulfides, including TNB and glutathione
CC persulfides. The likely in vivo substrates are di-, poly-, and
CC persulfide derivatives of coenzyme A, although polysulfide itself is
CC also efficiently reduced (PubMed:23530771). Shows coenzyme A disulfide
CC reductase (CoADR) activity with both NADH and NADPH, with a preference
CC for NADPH (PubMed:15720393). May also play a role in the reduction of
CC elemental sulfur (PubMed:23530771). {ECO:0000269|PubMed:15720393,
CC ECO:0000269|PubMed:23530771}.
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};
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:15720393, ECO:0000269|PubMed:23530771};
CC Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:23530771};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=73 uM for NADH {ECO:0000269|PubMed:15720393};
CC KM=20.5 uM for CoA persulfide (in the presence of NADH)
CC {ECO:0000269|PubMed:23530771};
CC KM=56.2 uM for CoA persulfide (in the presence of NADPH)
CC {ECO:0000269|PubMed:23530771};
CC KM=13.9 uM for NADH (in the presence of CoA persulfide)
CC {ECO:0000269|PubMed:23530771};
CC KM=12.7 uM for NADPH (in the presence of CoA persulfide)
CC {ECO:0000269|PubMed:23530771};
CC KM=94.9 uM for CoA polysulfide (in the presence of NADH)
CC {ECO:0000269|PubMed:23530771};
CC KM=125 uM for NADH (in the presence of CoA polysulfide)
CC {ECO:0000269|PubMed:23530771};
CC KM=14.1 uM for NADPH (in the presence of CoA polysulfide)
CC {ECO:0000269|PubMed:23530771};
CC KM=12.3 uM for polysulfide (in the presence of NADH)
CC {ECO:0000269|PubMed:23530771};
CC KM=25.1 uM for TNB persulfide (in the presence of NADH)
CC {ECO:0000269|PubMed:23530771};
CC KM=129 uM for DTNB (in the presence of NADH)
CC {ECO:0000269|PubMed:23530771};
CC Note=kcat is 1.11 sec(-1) with CoA persulfide as substrate (in the
CC presence of NADH). kcat is 1.50 sec(-1) with CoA persulfide as
CC substrate (in the presence of NADPH). kcat is 1.07 sec(-1) with NADH
CC as substrate (in the presence of CoA persulfide). kcat is 2.08 sec(-
CC 1) with NADPH as substrate (in the presence of CoA persulfide). kcat
CC is 6.56 sec(-1) with CoA polysulfide as substrate (in the presence of
CC NADH). kcat is 8.86 sec(-1) with NADH as substrate (in the presence
CC of CoA polysulfide). kcat is 16.1 sec(-1) with NADPH as substrate (in
CC the presence of CoA polysulfide). kcat is 1.04 sec(-1) with
CC polysulfide as substrate (in the presence of NADH). kcat is 3.37
CC sec(-1) with TNB persulfide as substrate (in the presence of NADH).
CC kcat is 0.69 sec(-1) with DTNB as substrate (in the presence of
CC NADH). {ECO:0000269|PubMed:23530771};
CC Temperature dependence:
CC Optimum temperature is 85 degrees Celsius. Thermostable.
CC {ECO:0000269|PubMed:15720393};
CC -!- SUBUNIT: Homodimer (PubMed:23530771). Homotetramer (PubMed:15720393).
CC {ECO:0000269|PubMed:15720393, ECO:0000269|PubMed:23530771}.
CC -!- DOMAIN: When compared to homologous enzymes known to reduce CoA
CC disulfide, this enzyme shows a narrower access channel for CoA
CC substrates, which suggests that this restriction might be responsible
CC for the enzyme's poor activity toward the bulky CoA disulfide substrate
CC (PubMed:23530771). The substrate channel was widened by making four
CC mutations along the channel wall (Y65A, Y66A, P67G, and H367G), leading
CC to a fourfold increase in kcat for the NAD(P)H-dependent reduction of
CC CoA disulfide and enhanced activity toward the substrate at lower
CC temperatures (PubMed:29988575). It suggests that substrate channel
CC morphology is an important determinant of substrate specificity for
CC this family of pyridine nucleotide disulfide oxidoreductase (PNDOR)
CC enzymes (PubMed:29988575). {ECO:0000269|PubMed:23530771,
CC ECO:0000269|PubMed:29988575}.
CC -!- SIMILARITY: Belongs to the class-III pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000305}.
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DR EMBL; BA000001; BAA29661.1; -; Genomic_DNA.
DR PIR; H71171; H71171.
DR PDB; 3KD9; X-ray; 2.75 A; A/B/C=7-444.
DR PDB; 4FX9; X-ray; 2.70 A; A/B=1-445.
DR PDB; 5L1N; X-ray; 3.60 A; A/B=1-445.
DR PDBsum; 3KD9; -.
DR PDBsum; 4FX9; -.
DR PDBsum; 5L1N; -.
DR AlphaFoldDB; O58308; -.
DR SMR; O58308; -.
DR STRING; 70601.3256978; -.
DR EnsemblBacteria; BAA29661; BAA29661; BAA29661.
DR KEGG; pho:PH0572; -.
DR eggNOG; arCOG01069; Archaea.
DR OMA; WVSHAPC; -.
DR BRENDA; 1.8.1.14; 5244.
DR SABIO-RK; O58308; -.
DR EvolutionaryTrace; O58308; -.
DR Proteomes; UP000000752; Chromosome.
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: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 3D-structure; FAD; Flavoprotein; NAD; NADP; Oxidoreductase;
KW Redox-active center.
FT CHAIN 1..445
FT /note="NAD(P)H coenzyme A polysulfide/persulfide reductase"
FT /id="PRO_0000184699"
FT ACT_SITE 48
FT /note="Redox-active"
FT /evidence="ECO:0000305|PubMed:23530771"
FT BINDING 16..17
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23530771,
FT ECO:0000269|PubMed:29988575, ECO:0007744|PDB:4FX9"
FT BINDING 27
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:23530771,
FT ECO:0000269|PubMed:29988575, ECO:0007744|PDB:4FX9"
FT BINDING 38..39
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23530771,
FT ECO:0000269|PubMed:29988575, ECO:0007744|PDB:4FX9"
FT BINDING 44..48
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:23530771,
FT ECO:0000269|PubMed:29988575, ECO:0007744|PDB:4FX9"
FT BINDING 45..47
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23530771,
FT ECO:0000269|PubMed:29988575, ECO:0007744|PDB:4FX9"
FT BINDING 65..66
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:23530771,
FT ECO:0007744|PDB:4FX9"
FT BINDING 75
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:23530771,
FT ECO:0000269|PubMed:29988575, ECO:0007744|PDB:4FX9"
FT BINDING 85
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23530771,
FT ECO:0000269|PubMed:29988575, ECO:0007744|PDB:4FX9"
FT BINDING 283
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23530771,
FT ECO:0000269|PubMed:29988575, ECO:0007744|PDB:4FX9"
FT BINDING 301
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23530771,
FT ECO:0007744|PDB:4FX9"
FT BINDING 305
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:23530771,
FT ECO:0000269|PubMed:29988575, ECO:0007744|PDB:4FX9"
FT BINDING 361
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:23530771,
FT ECO:0000269|PubMed:29988575, ECO:0007744|PDB:4FX9"
FT BINDING 425
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:23530771,
FT ECO:0000269|PubMed:29988575, ECO:0007744|PDB:4FX9"
FT BINDING 433
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:23530771,
FT ECO:0000269|PubMed:29988575, ECO:0007744|PDB:4FX9"
FT BINDING 441
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000269|PubMed:23530771,
FT ECO:0000269|PubMed:29988575, ECO:0007744|PDB:4FX9"
FT STRAND 8..12
FT /evidence="ECO:0007829|PDB:4FX9"
FT HELIX 16..28
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:4FX9"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:4FX9"
FT HELIX 50..54
FT /evidence="ECO:0007829|PDB:4FX9"
FT HELIX 60..63
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:4FX9"
FT HELIX 68..72
FT /evidence="ECO:0007829|PDB:4FX9"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 92..96
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 107..111
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:4FX9"
FT TURN 124..126
FT /evidence="ECO:0007829|PDB:4FX9"
FT HELIX 136..148
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 153..157
FT /evidence="ECO:0007829|PDB:4FX9"
FT HELIX 161..171
FT /evidence="ECO:0007829|PDB:4FX9"
FT TURN 172..174
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 182..185
FT /evidence="ECO:0007829|PDB:4FX9"
FT TURN 186..190
FT /evidence="ECO:0007829|PDB:4FX9"
FT HELIX 193..206
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 207..210
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 215..231
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 233..235
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 237..241
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:4FX9"
FT HELIX 250..253
FT /evidence="ECO:0007829|PDB:4FX9"
FT TURN 254..256
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 263..266
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:4FX9"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 285..289
FT /evidence="ECO:0007829|PDB:4FX9"
FT TURN 290..292
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:3KD9"
FT HELIX 301..315
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 329..333
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 336..342
FT /evidence="ECO:0007829|PDB:4FX9"
FT HELIX 345..350
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 355..365
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 367..370
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 374..382
FT /evidence="ECO:0007829|PDB:4FX9"
FT TURN 383..385
FT /evidence="ECO:0007829|PDB:4FX9"
FT STRAND 387..397
FT /evidence="ECO:0007829|PDB:4FX9"
FT HELIX 399..411
FT /evidence="ECO:0007829|PDB:4FX9"
FT HELIX 415..419
FT /evidence="ECO:0007829|PDB:4FX9"
FT TURN 427..429
FT /evidence="ECO:0007829|PDB:4FX9"
FT HELIX 435..443
FT /evidence="ECO:0007829|PDB:4FX9"
SQ SEQUENCE 445 AA; 48977 MW; 896A034000A0B233 CRC64;
MGENMKKKVV IIGGGAAGMS AASRVKRLKP EWDVKVFEAT EWVSHAPCGI PYVVEGLSTP
DKLMYYPPEV FIKKRGIDLH LNAEVIEVDT GYVRVRENGG EKSYEWDYLV FANGASPQVP
AIEGVNLKGV FTADLPPDAL AIREYMEKYK VENVVIIGGG YIGIEMAEAF AAQGKNVTMI
VRGERVLRRS FDKEVTDILE EKLKKHVNLR LQEITMKIEG EERVEKVVTD AGEYKAELVI
LATGIKPNIE LAKQLGVRIG ETGAIWTNEK MQTSVENVYA AGDVAETRHV ITGRRVWVPL
APAGNKMGYV AGSNIAGKEL HFPGVLGTAV TKFMDVEIGK TGLTEMEALK EGYDVRTAFI
KASTRPHYYP GGREIWLKGV VDNETNRLLG VQVVGSDILP RIDTAAAMLM AGFTTKDAFF
TDLAYAPPFA PVWDPLIVLA RVLKF
