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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
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
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
Ligand:  SPRi3
Resolution:  2.35Å
Species:  Human
References:  3
Enzyme Reaction Click here for help
EC Number:
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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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.


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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 21/07/2024. IUPHAR/BPS Guide to PHARMACOLOGY,