EzCatDB: S00329
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DB codeS00329
RLCP classification9.5010.536200.8010 : Hydride transfer
CATH domainDomain 13.40.50.720 : Rossmann foldCatalytic domain
E.C.1.1.1.153

CATH domainRelated DB codes (homologues)
3.40.50.720 : Rossmann foldS00543,S00551,S00552,S00553,S00602,S00604,S00605,S00608,S00610,S00625,S00319,S00328,S00330,S00331,S00332,D00456,D00457,D00458,S00324,S00320,S00325,S00326,S00327,D00459,S00335,S00336,S00334,T00219,S00339,D00513,D00001,D00002,D00003,D00005,D00007,D00008,D00010,D00012,D00017,D00018,D00023,D00027,D00028,D00031,D00032,D00033,D00034,D00035,D00037,D00048,D00071,D00476,D00481,D00482,D00490,D00492,D00494,D00545,D00601,D00603,D00604,D00605,D00615,D00845,D00857,D00858,M00161,M00171,M00210,T00002,T00010,T00011,T00015,T00227,T00247,T00408,T00414,D00827,D00262,D00274,D00275,M00035,T00109

Enzyme Name
UniProtKBKEGG

Q64105P35270
Protein nameSepiapterin reductaseSepiapterin reductasesepiapterin reductase
SR
SynonymsSPR
EC 1.1.1.153
SPR
EC 1.1.1.153
RefSeq
NP_003115.1 (Protein)
NM_003124.4 (DNA/RNA sequence)
PfamPF00106 (adh_short)
[Graphical view]
PF00106 (adh_short)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00790Folate biosynthesis

UniProtKB:Accession NumberQ64105P35270
Entry nameSPRE_MOUSESPRE_HUMAN
Activity7,8-dihydrobiopterin + NADP(+) = sepiapterin + NADPH.,Tetrahydrobiopterin + 2 NADP(+) = 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH.7,8-dihydrobiopterin + NADP(+) = sepiapterin + NADPH.,Tetrahydrobiopterin + 2 NADP(+) = 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH.
SubunitHomodimer.Homodimer.
Subcellular locationCytoplasm.Cytoplasm.
Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00835C00005C00080C03684C02953C00006C00272I00093I00094
CompoundSepiapterinNADPHH+6-pyruvoyl-5,6,7,8-tetrahydropterin7,8-DihydrobiopterinNADP+Tetrahydrobiopterin6-(1'-hydroxy-2'-oxopropyl)-tetrahydropterin6-lactoyl-tetrahydropterin
Typeamide group,amine group,imine group,carbohydrateamide group,amine group,nucleotideothersamide group,amine group,aromatic ring (with nitrogen atoms),carbohydrateamide group,amine group,aromatic ring (with nitrogen atoms),carbohydrateamide group,amine group,nucleotideamide group,amine group,aromatic ring (with nitrogen atoms),carbohydrate

ChEBI
16474
15378
17804
43029
64277
18009
59560


PubChem65253
5884
1038
128973
252
119055
5886
44257


                 
1nasAUnboundUnbound UnboundUnboundBound:NAPUnboundUnboundUnbound
1oaaAUnboundUnbound UnboundUnboundBound:NAPUnboundUnboundUnbound
1sepAAnalogue:BIOUnbound UnboundUnboundBound:NAPUnboundUnboundUnbound
1z6zAUnboundUnbound UnboundUnboundBound:NAPUnboundUnboundUnbound
1z6zBUnboundUnbound UnboundUnboundBound:NAPUnboundUnboundUnbound
1z6zCUnboundUnbound UnboundUnboundBound:NAPUnboundUnboundUnbound
1z6zDUnboundUnbound UnboundUnboundBound:NAPUnboundUnboundUnbound
1z6zEUnboundUnbound UnboundUnboundBound:NAPUnboundUnboundUnbound
1z6zFUnboundUnbound UnboundUnboundBound:NAPUnboundUnboundUnbound

Active-site residues
resource
literature [10] & [13]
pdbCatalytic residues
         
1nasASER 158;TYR 171;LYS 175
1oaaASER 158;TYR 171;LYS 175
1sepASER 158;TYR 171;LYS 175
1z6zASER 154;TYR 167;LYS 171
1z6zBSER 154;TYR 167;LYS 171
1z6zCSER 154;TYR 167;LYS 171
1z6zDSER 154;TYR 167;LYS 171
1z6zESER 154;TYR 167;LYS 171
1z6zFSER 154;TYR 167;LYS 171

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[7]p.7224-7225
[8]Fig.11
[10]p.311-313
[12]Fig.5

references
[1]
PubMed ID7046745
JournalBiochem Biophys Res Commun
Year1982
Volume105
Pages75-81
AuthorsKatoh S, Sueoka T, Yamada S
TitleDirect inhibition of brain sepiapterin reductase by a catecholamine and an indoleamine.
[2]
PubMed ID3888282
JournalBiochim Biophys Acta
Year1985
Volume840
Pages235-44
AuthorsMasada M, Akino M, Sueoka T, Katoh S
TitleDyspropterin, an intermediate formed from dihydroneopterin triphosphate in the biosynthetic pathway of tetrahydrobiopterin.
[3]
PubMed ID3888618
JournalEur J Biochem
Year1985
Volume148
Pages413-9
AuthorsCurtius HC, Heintel D, Ghisla S, Kuster T, Leimbacher W, Niederwieser A
TitleTetrahydrobiopterin biosynthesis. Studies with specifically labeled (2H)NAD(P)H and 2H2O and of the enzymes involved.
[4]
PubMed ID3553175
JournalJ Biochem (Tokyo)
Year1987
Volume101
Pages275-8
AuthorsKatoh S, Sueoka T
TitleIsomerization of 6-lactoyl tetrahydropterin by sepiapterin reductase.
[5]
PubMed ID1544933
JournalJ Biol Chem
Year1992
Volume267
Pages5599-607
AuthorsSmith GK, Duch DS, Edelstein MP, Bigham EC
TitleNew inhibitors of sepiapterin reductase. Lack of an effect of intracellular tetrahydrobiopterin depletion upon in vitro proliferation of two human cell lines.
[6]
PubMed ID9165069
JournalBiol Chem
Year1997
Volume378
Pages185-92
AuthorsAuerbach G, Nar H
TitleThe pathway from GTP to tetrahydrobiopterin: three-dimensional structures of GTP cyclohydrolase I and 6-pyruvoyl tetrahydropterin synthase.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS)
Medline ID98070299
PubMed ID9405351
JournalEMBO J
Year1997
Volume16
Pages7219-30
AuthorsAuerbach G, Herrmann A, Gutlich M, Fischer M, Jacob U, Bacher A, Huber R
TitleThe 1.25 A crystal structure of sepiapterin reductase reveals its binding mode to pterins and brain neurotransmitters.
Related PDB1nas,1oaa,1sep
Related UniProtKBQ64105
[8]
PubMed ID9774432
JournalJ Biol Chem
Year1998
Volume273
Pages28132-41
AuthorsBracher A, Eisenreich W, Schramek N, Ritz H, Gotze E, Herrmann A, Gutlich M, Bacher A
TitleBiosynthesis of pteridines. NMR studies on the reaction mechanisms of GTP cyclohydrolase I, pyruvoyltetrahydropterin synthase, and sepiapterin reductase.
[9]
PubMed ID10333495
JournalBiochem J
Year1999
Volume340
Pages497-503
AuthorsCho SH, Na JU, Youn H, Hwang CS, Lee CH, Kang SO
TitleSepiapterin reductase producing L-threo-dihydrobiopterin from Chlorobium tepidum.
[10]
PubMed ID10350607
JournalBiochim Biophys Acta
Year1999
Volume1431
Pages306-14
AuthorsFujimoto K, Ichinose H, Nagatsu T, Nonaka T, Mitsui Y, Katoh S
TitleFunctionally important residues tyrosine-171 and serine-158 in sepiapterin reductase.
[11]
PubMed ID10727395
JournalBiochem J
Year2000
Volume347 Pt 1
Pages1-16
AuthorsThony B, Auerbach G, Blau N
TitleTetrahydrobiopterin biosynthesis, regeneration and functions.
[12]
PubMed ID11306098
JournalChem Biol Interact
Year2001
Volume130-132
Pages825-32
AuthorsFujimoto K, Hara M, Yamada H, Sakurai M, Inaba A, Tomomura A, Katoh S
TitleRole of the conserved Ser-Tyr-Lys triad of the SDR family in sepiapterin reductase.

comments
This enzyme belongs to the short-chain dehydrogenase/reductase (SDR) superfamily, along with Drosophia alcohol dehydrogenase (S00319 in EzCatDB). This enzyme has got a catalytic triad composed of conserved residues, Ser, Tyr, and Lys. The conformation of these residues, compared to that of the NAD molecule, seems to be similar to that of the homologous enzymes. Thus, its catalytic mechanism must be similar to those of the homologous enzymes.
According to the literature [7] and [11], this enzyme catalyzes three reactions, including the two reduction steps for the diketo substrate (C03684), as follows:
(A) Reduction of C1'-keto group of the substrate by NADPH, forming 1'-hydroxyl intermediate (I00093):
(B) Isomerization of 1'-hydroxyl intermediate, forming 1'-keto-2'hydroxyl intermediate (I00094):
(C) Reduction of C1'-keto group of the intermediate by NADPH:
The first and last reactions must be catalyzed by the catalytic triad, as in the other homologous enzymes.

createdupdated
2004-03-092011-06-28


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