SPR
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSPR, SDR38C1, sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase), sepiapterin reductase
External IDsOMIM: 182125 MGI: 103078 HomoloGene: 37735 GeneCards: SPR
Orthologs
SpeciesHumanMouse
Entrez

6697

20751

Ensembl

ENSG00000116096

ENSMUSG00000033735

UniProt

P35270

Q64105

RefSeq (mRNA)

NM_003124

NM_011467

RefSeq (protein)

NP_003115

n/a

Location (UCSC)Chr 2: 72.89 – 72.89 MbChr 6: 85.11 – 85.11 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Sepiapterin reductase is an enzyme that in humans is encoded by the SPR gene.[5][6][7]

Function

Sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase; EC 1.1.1.153) catalyzes the NADPH-dependent reduction of various carbonyl substances, including derivatives of pteridines, and belongs to a group of enzymes called aldo-keto reductases. SPR plays an important role in the biosynthesis of tetrahydrobiopterin.[7]

Reaction

sepiapterin reductase
Sepiapterin reductase homodimer, Human
Identifiers
EC no.1.1.1.153
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins

Sepiapterin reductase (SPR) catalyzes the chemical reaction

L-erythro-7,8-dihydrobiopterin + NADP+ sepiapterin + NADPH + H+

Thus, the two substrates of this enzyme are L-erythro-7,8-dihydrobiopterin and NADP+, whereas its three products are sepiapterin, NADPH, and a single hydrogen ion (H+).

This enzyme belongs to the family of oxidoreductases, to be specific, those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 7,8-dihydrobiopterin:NADP+ oxidoreductase. This enzyme participates in folate biosynthesis.

[8]

Clinical significance

Mutations of the SPR gene may cause sepiapterin reductase deficiency, a rare disease. The clinical phenotype can include progressive psychomotor retardation, altered tone, seizures, choreoathetosis, temperature instability, hypersalivation, microcephaly, and irritability. Patients with sepiapterin reductase deficiency also manifest dystonia with diurnal variation, oculogyric crises, tremor, hypersomnolence, oculomotor apraxia, and weakness.[9] Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).[10]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000116096 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000033735 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Ichinose H, Katoh S, Sueoka T, Titani K, Fujita K, Nagatsu T (Oct 1991). "Cloning and sequencing of cDNA encoding human sepiapterin reductase--an enzyme involved in tetrahydrobiopterin biosynthesis". Biochem Biophys Res Commun. 179 (1): 183–189. doi:10.1016/0006-291X(91)91352-D. PMID 1883349.
  6. Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jornvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U (Feb 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chem Biol Interact. 178 (1–3): 94–98. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726.
  7. 1 2 "Entrez Gene: SPR sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase)".
  8. "BRENDA - Information on EC 1.1.1.153 - sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)".
  9. Pearl PL, Taylor JL, Trzcinski S, Sokohl A (May 2007). "The pediatric neurotransmitter disorders". J Child Neurol. 22 (5): 606–616. doi:10.1177/0883073807302619. PMID 17690069. S2CID 10689202.
  10. "Patient registry".

Further reading

  • Overview of all the structural information available in the PDB for UniProt: P35270 (Human Sepiapterin reductase) at the PDBe-KB.
  • Overview of all the structural information available in the PDB for UniProt: Q64105 (Mouse Sepiapterin reductase) at the PDBe-KB.
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