SPRE_CHLTE
ID SPRE_CHLTE Reviewed; 244 AA.
AC Q8KES3;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Sepiapterin reductase {ECO:0000312|EMBL:AAM71851.1};
DE Short=SPR {ECO:0000250|UniProtKB:Q64105};
DE Short=cSR {ECO:0000303|PubMed:18542834};
DE EC=1.1.1.325 {ECO:0000269|PubMed:10333495, ECO:0000269|PubMed:15621425};
GN OrderedLocusNames=CT0609;
OS Chlorobaculum tepidum (strain ATCC 49652 / DSM 12025 / NBRC 103806 / TLS)
OS (Chlorobium tepidum).
OC Bacteria; Chlorobi; Chlorobia; Chlorobiales; Chlorobiaceae; Chlorobaculum.
OX NCBI_TaxID=194439;
RN [1] {ECO:0000312|EMBL:AAM71851.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 49652 / DSM 12025 / NBRC 103806 / TLS;
RX PubMed=12093901; DOI=10.1073/pnas.132181499;
RA Eisen J.A., Nelson K.E., Paulsen I.T., Heidelberg J.F., Wu M., Dodson R.J.,
RA DeBoy R.T., Gwinn M.L., Nelson W.C., Haft D.H., Hickey E.K., Peterson J.D.,
RA Durkin A.S., Kolonay J.F., Yang F., Holt I.E., Umayam L.A., Mason T.M.,
RA Brenner M., Shea T.P., Parksey D.S., Nierman W.C., Feldblyum T.V.,
RA Hansen C.L., Craven M.B., Radune D., Vamathevan J.J., Khouri H.M.,
RA White O., Gruber T.M., Ketchum K.A., Venter J.C., Tettelin H., Bryant D.A.,
RA Fraser C.M.;
RT "The complete genome sequence of Chlorobium tepidum TLS, a photosynthetic,
RT anaerobic, green-sulfur bacterium.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:9509-9514(2002).
RN [2] {ECO:0000305}
RP PROTEIN SEQUENCE OF 1-30, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND
RP SUBUNIT.
RX PubMed=10333495; DOI=10.1042/bj3400497;
RA Cho S.H., Na J.U., Youn H., Hwang C.S., Lee C.H., Kang S.O.;
RT "Sepiapterin reductase producing L-threo-dihydrobiopterin from Chlorobium
RT tepidum.";
RL Biochem. J. 340:497-503(1999).
RN [3] {ECO:0000305}
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15621425; DOI=10.1016/j.femsle.2004.10.044;
RA Choi Y.K., Jun S.R., Cha E.Y., Park J.S., Park Y.S.;
RT "Sepiapterin reductases from Chlorobium tepidum and Chlorobium limicola
RT catalyze the synthesis of L-threo-tetrahydrobiopterin from 6-
RT pyruvoyltetrahydropterin.";
RL FEMS Microbiol. Lett. 242:95-99(2005).
RN [4] {ECO:0000305}
RP BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND
RP MUTAGENESIS OF PHE-99 AND TRP-196.
RX PubMed=18542834; DOI=10.1111/j.1745-7270.2008.00422.x;
RA Supangat S., Park S.O., Seo K.H., Lee S.Y., Park Y.S., Lee K.H.;
RT "Role of Phe-99 and Trp-196 of sepiapterin reductase from Chlorobium
RT tepidum in the production of L-threo-tetrahydrobiopterin.";
RL Acta Biochim. Biophys. Sin. 40:513-518(2008).
RN [5] {ECO:0000305, ECO:0000312|PDB:2BD0}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF APOPROTEIN AND IN COMPLEX WITH
RP BIOPTERIN AND NADP, AND SUBUNIT.
RX PubMed=16308317; DOI=10.1074/jbc.m509343200;
RA Supangat S., Seo K.H., Choi Y.K., Park Y.S., Son D., Han C.D., Lee K.H.;
RT "Structure of Chlorobium tepidum sepiapterin reductase complex reveals the
RT novel substrate binding mode for stereospecific production of L-threo-
RT tetrahydrobiopterin.";
RL J. Biol. Chem. 281:2249-2256(2006).
CC -!- FUNCTION: Catalyzes the final reductions in tetra-hydrobiopterin
CC biosynthesis to form 5,6,7,8-tetrahydrobiopterin.
CC {ECO:0000269|PubMed:10333495, ECO:0000269|PubMed:15621425,
CC ECO:0000269|PubMed:18542834}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-threo-7,8-dihydrobiopterin + NADP(+) = H(+) + NADPH +
CC sepiapterin; Xref=Rhea:RHEA:32619, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16095, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:64240; EC=1.1.1.325;
CC Evidence={ECO:0000269|PubMed:10333495, ECO:0000269|PubMed:15621425};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-threo-tetrahydrobiopterin + 2 NADP(+) = 6-pyruvoyl-5,6,7,8-
CC tetrahydropterin + 2 H(+) + 2 NADPH; Xref=Rhea:RHEA:32623,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:64241, ChEBI:CHEBI:136564; EC=1.1.1.325;
CC Evidence={ECO:0000269|PubMed:15621425};
CC -!- ACTIVITY REGULATION: Slightly inhibited by N-acetyldopamine but not by
CC N-acetylserotonin or melatonin. {ECO:0000269|PubMed:10333495}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=21 uM for sepiapterin (at pH 8.8 and 45 degrees Celsius)
CC {ECO:0000269|PubMed:10333495, ECO:0000269|PubMed:18542834};
CC KM=0.18 uM for sepiapterin (at pH 6.5 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:10333495, ECO:0000269|PubMed:18542834};
CC KM=6.2 uM for NADPH (at pH 8.8 and 45 degrees Celsius)
CC {ECO:0000269|PubMed:10333495, ECO:0000269|PubMed:18542834};
CC Vmax=12.0 pmol/min/mg enzyme for the reverse reaction reducing
CC sepapterin (at 37 degrees Celsius) {ECO:0000269|PubMed:10333495,
CC ECO:0000269|PubMed:18542834};
CC Note=For the reverse reaction, accepts L-threo-dihydrobiopterin, D-
CC threo-dihydrobiopterin, L-threo-dihydroneopterin, dihydrotepidopterin
CC and L-erythro-dihydrobiopterin as substrates.
CC {ECO:0000269|PubMed:10333495};
CC pH dependence:
CC Optimum pH is around 8.8. Activity drops sharply above and below the
CC optimum and is absent at pH 3 and virtually so at pH 10.6.
CC {ECO:0000269|PubMed:10333495, ECO:0000269|PubMed:18542834};
CC Temperature dependence:
CC Optimum temperature is 50 degrees Celsius. Stable at 25 and 50
CC degrees Celsius for 2 h but loses activity at 70 degrees Celsius in
CC 20 min. {ECO:0000269|PubMed:10333495, ECO:0000269|PubMed:18542834};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10333495,
CC ECO:0000269|PubMed:16308317, ECO:0000269|PubMed:18542834}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10333495}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000250|UniProtKB:Q64105}.
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DR EMBL; AE006470; AAM71851.1; -; Genomic_DNA.
DR RefSeq; NP_661509.1; NC_002932.3.
DR RefSeq; WP_010932296.1; NC_002932.3.
DR PDB; 2BD0; X-ray; 1.70 A; A/B/C/D=1-244.
DR PDBsum; 2BD0; -.
DR AlphaFoldDB; Q8KES3; -.
DR SMR; Q8KES3; -.
DR STRING; 194439.CT0609; -.
DR EnsemblBacteria; AAM71851; AAM71851; CT0609.
DR KEGG; cte:CT0609; -.
DR PATRIC; fig|194439.7.peg.566; -.
DR eggNOG; COG4221; Bacteria.
DR HOGENOM; CLU_010194_2_10_10; -.
DR OMA; VMMMPED; -.
DR OrthoDB; 1261526at2; -.
DR BioCyc; MetaCyc:MON-13404; -.
DR EvolutionaryTrace; Q8KES3; -.
DR Proteomes; UP000001007; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; NADP;
KW Nucleotide-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..244
FT /note="Sepiapterin reductase"
FT /id="PRO_0000424153"
FT BINDING 9..15
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:16308317"
FT BINDING 40..42
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:16308317"
FT BINDING 66..67
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:16308317"
FT BINDING 93
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:16308317"
FT BINDING 99
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:16308317"
FT BINDING 116
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:16308317"
FT BINDING 145
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:16308317"
FT BINDING 158
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:16308317"
FT BINDING 158
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:16308317"
FT BINDING 162
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:16308317"
FT BINDING 191..196
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:16308317"
FT BINDING 196
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:16308317"
FT MUTAGEN 99
FT /note="F->A: Drastically reduces activity. Complete loss of
FT activity; when associated with A-196."
FT /evidence="ECO:0000269|PubMed:18542834"
FT MUTAGEN 196
FT /note="W->A: Drastically reduces activity. Complete loss of
FT activity; when associated with A-99."
FT /evidence="ECO:0000269|PubMed:18542834"
FT STRAND 3..8
FT /evidence="ECO:0007829|PDB:2BD0"
FT TURN 9..11
FT /evidence="ECO:0007829|PDB:2BD0"
FT HELIX 13..25
FT /evidence="ECO:0007829|PDB:2BD0"
FT TURN 26..28
FT /evidence="ECO:0007829|PDB:2BD0"
FT STRAND 34..41
FT /evidence="ECO:0007829|PDB:2BD0"
FT HELIX 43..54
FT /evidence="ECO:0007829|PDB:2BD0"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:2BD0"
FT STRAND 59..64
FT /evidence="ECO:0007829|PDB:2BD0"
FT HELIX 70..83
FT /evidence="ECO:0007829|PDB:2BD0"
FT STRAND 88..92
FT /evidence="ECO:0007829|PDB:2BD0"
FT HELIX 102..104
FT /evidence="ECO:0007829|PDB:2BD0"
FT HELIX 107..117
FT /evidence="ECO:0007829|PDB:2BD0"
FT HELIX 119..135
FT /evidence="ECO:0007829|PDB:2BD0"
FT STRAND 138..143
FT /evidence="ECO:0007829|PDB:2BD0"
FT HELIX 146..148
FT /evidence="ECO:0007829|PDB:2BD0"
FT HELIX 156..176
FT /evidence="ECO:0007829|PDB:2BD0"
FT TURN 177..180
FT /evidence="ECO:0007829|PDB:2BD0"
FT STRAND 181..188
FT /evidence="ECO:0007829|PDB:2BD0"
FT TURN 194..196
FT /evidence="ECO:0007829|PDB:2BD0"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:2BD0"
FT HELIX 210..221
FT /evidence="ECO:0007829|PDB:2BD0"
FT STRAND 227..236
FT /evidence="ECO:0007829|PDB:2BD0"
SQ SEQUENCE 244 AA; 27114 MW; 754CE7BC0363D9DA CRC64;
MKHILLITGA GKGIGRAIAL EFARAARHHP DFEPVLVLSS RTAADLEKIS LECRAEGALT
DTITADISDM ADVRRLTTHI VERYGHIDCL VNNAGVGRFG ALSDLTEEDF DYTMNTNLKG
TFFLTQALFA LMERQHSGHI FFITSVAATK AFRHSSIYCM SKFGQRGLVE TMRLYARKCN
VRITDVQPGA VYTPMWGKVD DEMQALMMMP EDIAAPVVQA YLQPSRTVVE EIILRPTSGD
IQDD
