6j3c
Crystal structure of human DHODH in complex with inhibitor 1291Crystal structure of human DHODH in complex with inhibitor 1291
Structural highlights
Disease[PYRD_HUMAN] Defects in DHODH are the cause of postaxial acrofacial dysostosis (POADS) [MIM:263750]; also known as Miller syndrome. POADS is characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. POADS is a very rare disorder: only 2 multiplex families, each consisting of 2 affected siblings born to unaffected, nonconsanguineous parents, have been described among a total of around 30 reported cases.[1] Function[PYRD_HUMAN] Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor. Publication Abstract from PubMedHuman dihydroorotate dehydrogenase (DHODH), the enzyme that catalyzes the rate-limiting step in de novo pyrimidine biosynthesis, is considered to be an attractive target for potential treatment of autoimmune disease and cancer. Here, we present a novel class of human DHODH inhibitors with high inhibitory potency. The high-resolution crystal structures of human DHODH complexed with various agents reveal the details of their interactions. Comparisons with the binding modes of teriflunomide and brequinar provide insights that may facilitate the development of new inhibitors targeting human DHODH. A novel series of human dihydroorotate dehydrogenase inhibitors discovered by in vitro screening: inhibition activity and crystallographic binding mode.,Zeng T, Zuo Z, Luo Y, Zhao Y, Yu Y, Chen Q FEBS Open Bio. 2019 Aug;9(8):1348-1354. doi: 10.1002/2211-5463.12658. Epub 2019, May 29. PMID:31087527[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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