DB code: S00329

RLCP classification 9.5010.536200.8010 : Hydride transfer
CATH domain 3.40.50.720 : Rossmann fold Catalytic domain
E.C. 1.1.1.153
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.720 : Rossmann fold S00543 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam RefSeq
Q64105 Sepiapterin reductase
SPR
EC 1.1.1.153
PF00106 (adh_short)
[Graphical View]
P35270 Sepiapterin reductase
SPR
EC 1.1.1.153
PF00106 (adh_short)
[Graphical View] 		NP_003115.1 (Protein)
NM_003124.4 (DNA/RNA sequence)

KEGG enzyme name
sepiapterin reductase
SR

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q64105 SPRE_MOUSE 7,8-dihydrobiopterin + NADP(+) = sepiapterin + NADPH. Tetrahydrobiopterin + 2 NADP(+) = 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH. Homodimer. Cytoplasm.
P35270 SPRE_HUMAN 7,8-dihydrobiopterin + NADP(+) = sepiapterin + NADPH. Tetrahydrobiopterin + 2 NADP(+) = 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH. Homodimer. Cytoplasm.

KEGG Pathways
Map code Pathways E.C.
MAP00790 Folate biosynthesis

Compound table
Substrates Products Intermediates
KEGG-id C00835 C00005 C00080 C03684 C02953 C00006 C00272 I00093 I00094
E.C.
Compound Sepiapterin NADPH H+ 6-pyruvoyl-5,6,7,8-tetrahydropterin 7,8-Dihydrobiopterin NADP+ Tetrahydrobiopterin 6-(1'-hydroxy-2'-oxopropyl)-tetrahydropterin 6-lactoyl-tetrahydropterin
Type amide group,amine group,imine group,carbohydrate amide group,amine group,nucleotide others amide group,amine group,aromatic ring (with nitrogen atoms),carbohydrate amide group,amine group,aromatic ring (with nitrogen atoms),carbohydrate amide group,amine group,nucleotide amide group,amine group,aromatic ring (with nitrogen atoms),carbohydrate
ChEBI 16474
 16474
 		15378
 15378
 		17804
 17804
 		43029
 64277
 43029
 64277
 		18009
 18009
 		59560
 59560
PubChem 65253
 65253
 		5884
 5884
 		1038
 1038
 		128973
 128973
 		119055
 252
 119055
 252
 		5886
 5886
 		44257
 44257
1nasA Unbound Unbound Unbound Unbound Bound:NAP Unbound Unbound Unbound
1oaaA Unbound Unbound Unbound Unbound Bound:NAP Unbound Unbound Unbound
1sepA Analogue:BIO Unbound Unbound Unbound Bound:NAP Unbound Unbound Unbound
1z6zA Unbound Unbound Unbound Unbound Bound:NAP Unbound Unbound Unbound
1z6zB Unbound Unbound Unbound Unbound Bound:NAP Unbound Unbound Unbound
1z6zC Unbound Unbound Unbound Unbound Bound:NAP Unbound Unbound Unbound
1z6zD Unbound Unbound Unbound Unbound Bound:NAP Unbound Unbound Unbound
1z6zE Unbound Unbound Unbound Unbound Bound:NAP Unbound Unbound Unbound
1z6zF Unbound Unbound Unbound Unbound Bound:NAP Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [10] & [13]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1nasA SER 158;TYR 171;LYS 175
1oaaA SER 158;TYR 171;LYS 175
1sepA SER 158;TYR 171;LYS 175
1z6zA SER 154;TYR 167;LYS 171
1z6zB SER 154;TYR 167;LYS 171
1z6zC SER 154;TYR 167;LYS 171
1z6zD SER 154;TYR 167;LYS 171
1z6zE SER 154;TYR 167;LYS 171
1z6zF SER 154;TYR 167;LYS 171

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[7]
p.7224-7225
[8]
Fig.11
[10]
p.311-313
[12]
Fig.5

References
[1]
Resource
Comments
Medline ID
PubMed ID 7046745
Journal Biochem Biophys Res Commun
Year 1982
Volume 105
Pages 75-81
Authors Katoh S, Sueoka T, Yamada S
Title Direct inhibition of brain sepiapterin reductase by a catecholamine and an indoleamine.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 3888282
Journal Biochim Biophys Acta
Year 1985
Volume 840
Pages 235-44
Authors Masada M, Akino M, Sueoka T, Katoh S
Title Dyspropterin, an intermediate formed from dihydroneopterin triphosphate in the biosynthetic pathway of tetrahydrobiopterin.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 3888618
Journal Eur J Biochem
Year 1985
Volume 148
Pages 413-9
Authors Curtius HC, Heintel D, Ghisla S, Kuster T, Leimbacher W, Niederwieser A
Title Tetrahydrobiopterin biosynthesis. Studies with specifically labeled (2H)NAD(P)H and 2H2O and of the enzymes involved.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 3553175
Journal J Biochem (Tokyo)
Year 1987
Volume 101
Pages 275-8
Authors Katoh S, Sueoka T
Title Isomerization of 6-lactoyl tetrahydropterin by sepiapterin reductase.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 1544933
Journal J Biol Chem
Year 1992
Volume 267
Pages 5599-607
Authors Smith GK, Duch DS, Edelstein MP, Bigham EC
Title New inhibitors of sepiapterin reductase. Lack of an effect of intracellular tetrahydrobiopterin depletion upon in vitro proliferation of two human cell lines.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9165069
Journal Biol Chem
Year 1997
Volume 378
Pages 185-92
Authors Auerbach G, Nar H
Title The pathway from GTP to tetrahydrobiopterin: three-dimensional structures of GTP cyclohydrolase I and 6-pyruvoyl tetrahydropterin synthase.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS)
Medline ID 98070299
PubMed ID 9405351
Journal EMBO J
Year 1997
Volume 16
Pages 7219-30
Authors Auerbach G, Herrmann A, Gutlich M, Fischer M, Jacob U, Bacher A, Huber R
Title The 1.25 A crystal structure of sepiapterin reductase reveals its binding mode to pterins and brain neurotransmitters.
Related PDB 1nas 1oaa 1sep
Related UniProtKB Q64105
[8]
Resource
Comments
Medline ID
PubMed ID 9774432
Journal J Biol Chem
Year 1998
Volume 273
Pages 28132-41
Authors Bracher A, Eisenreich W, Schramek N, Ritz H, Gotze E, Herrmann A, Gutlich M, Bacher A
Title Biosynthesis of pteridines. NMR studies on the reaction mechanisms of GTP cyclohydrolase I, pyruvoyltetrahydropterin synthase, and sepiapterin reductase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 10333495
Journal Biochem J
Year 1999
Volume 340
Pages 497-503
Authors Cho SH, Na JU, Youn H, Hwang CS, Lee CH, Kang SO
Title Sepiapterin reductase producing L-threo-dihydrobiopterin from Chlorobium tepidum.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 10350607
Journal Biochim Biophys Acta
Year 1999
Volume 1431
Pages 306-14
Authors Fujimoto K, Ichinose H, Nagatsu T, Nonaka T, Mitsui Y, Katoh S
Title Functionally important residues tyrosine-171 and serine-158 in sepiapterin reductase.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 10727395
Journal Biochem J
Year 2000
Volume 347 Pt 1
Pages 1-16
Authors Thony B, Auerbach G, Blau N
Title Tetrahydrobiopterin biosynthesis, regeneration and functions.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 11306098
Journal Chem Biol Interact
Year 2001
Volume 130-132
Pages 825-32
Authors Fujimoto K, Hara M, Yamada H, Sakurai M, Inaba A, Tomomura A, Katoh S
Title Role of the conserved Ser-Tyr-Lys triad of the SDR family in sepiapterin reductase.
Related PDB
Related UniProtKB

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.

Created Updated
2004-03-09 2011-06-28