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sepiapterin reductase

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 3020

Nomenclature: sepiapterin reductase

Family: 1.-.-.- Oxidoreductases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 261 2p13.2 SPR sepiapterin reductase
Mouse - 262 6 C3; 6 37.15 cM Spr sepiapterin reductase
Rat - 262 4q34 Spr sepiapterin reductase
Previous and Unofficial Names Click here for help
SDR38C1 | sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming) | short chain dehydrogenase/reductase family 38C, member 1
Database Links Click here for help
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BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
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RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human sepiapterin reductase in complex with an N-acetylserotinin analogue
PDB Id:  4XWY
Ligand:  SPRi3
Resolution:  2.35Å
Species:  Human
References:  3
Enzyme Reaction Click here for help
EC Number: 1.1.1.153
Description Reaction Reference
De novo synthesis of tetrahydrobiopterin from GTP, and synthesis of the erythro form of tetrahydrobiopterin L-erythro-7,8-dihydrobiopterin + NADP(+) <=> sepiapterin + NADPH
L-erythro-tetrahydrobiopterin + 2 NADP(+) <=> 6-pyruvoyl-5,6,7,8-tetrahydropterin + 2 NADPH

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
SPRi3 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.0 pIC50 1
pIC50 8.0 (IC50 1.1x10-8 M) [1]
Description: In a chromogenic cell-free enzyme assay.
Immunopharmacology Comments
BH4 has been reported as a crucial regulator of T cell function and proliferation [2]. As a result, modulation of enzymes in the BH4 biosynthesis pathway has been suggested as a novel mechanistic approach for the treatment of autoimmune diseases (pathway inhibitors to reduce T cell activity) and anticancer immunity (pathway activators to enhance T cell effector function). In support of this hypothesis, the sepiapterin reductase (SPR; the terminal enzyme in BH4 biosynthesis) inhibitor SPRi3, has been shown to reduce neuropathic and inflammatory pain in vivo [3].
General Comments
SPR is an aldo-keto reductase that catalyses the terminal reaction in the biosynthesis of tetrahydrobiopterin (BH4, sapropterin) from GTP.

References

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1. Blagg J. (2011) Sepiapterin reductase inhibitors for the treatment of pain. Patent number: WO2011047156A1. Assignee: Hercules Technology Management Co V, Inc.. Priority date: 15/10/2009. Publication date: 21/04/2011.

2. Cronin SJF, Seehus C, Weidinger A, Talbot S, Reissig S, Seifert M, Pierson Y, McNeill E, Longhi MS, Turnes BL et al.. (2018) The metabolite BH4 controls T cell proliferation in autoimmunity and cancer. Nature, 563 (7732): 564-568. [PMID:30405245]

3. Latremoliere A, Latini A, Andrews N, Cronin SJ, Fujita M, Gorska K, Hovius R, Romero C, Chuaiphichai S, Painter M et al.. (2015) Reduction of Neuropathic and Inflammatory Pain through Inhibition of the Tetrahydrobiopterin Pathway. Neuron, 86 (6): 1393-406. [PMID:26087165]

How to cite this page

1.-.-.- Oxidoreductases: sepiapterin reductase. Last modified on 12/11/2018. Accessed on 28/11/2022. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=3020.