6usn
Co-crystal structure of SPR with compound 5
Structural highlights
DiseaseSPRE_HUMAN Defects in SPR are the cause of dystonia DOPA-responsive due to sepiapterin reductase deficiency (DRDSPRD) [MIM:612716. In the majority of cases, patients manifest progressive psychomotor retardation, dystonia and spasticity. Cognitive anomalies are also often present. The disease is due to severe dopamine and serotonin deficiencies in the central nervous system caused by a defect in BH4 synthesis. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures.[1] [2] [3] FunctionSPRE_HUMAN Catalyzes the final one or two reductions in tetra-hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin. Publication Abstract from PubMedSepiapterin reductase has been identified as a potential drug target for neuropathic and inflammatory pain. Virtual screening was executed against a publicly available x-ray crystal structure of sepiapterin reductase. A set of structurally diverse and potent sepiapterin reductase inhibitors was identified. This set of compounds with favorable ligand efficiency and lipophilic efficiency are tractable for further optimization. An SAR follow-up library was synthesized based on one of the virtual screening hits exploring SAR. Virtual screening to identify potent sepiapterin reductase inhibitors.,Gao H, Schneider S, Andrews P, Wang K, Huang X, Sparling BA Bioorg Med Chem Lett. 2019 Nov 9:126793. doi: 10.1016/j.bmcl.2019.126793. PMID:31740247[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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