6t85 | pdb_00006t85
Urocanate reductase in complex with ADP
Structural highlights
Function[URDA_SHEON] Catalyzes the two-electron reduction of urocanate to dihydrourocanate (also named imidazole propionate or deamino-histidine). The physiological electron donor is unknown; it might be the membrane-bound tetraheme cytochrome c (CymA). Enables anaerobic growth with urocanate as a sole terminal electron acceptor, and thus can provide the cells with a niche where no other bacteria can compete and survive. Is unable to reduce cinnamate and other unsaturated organic acids such as acrylic, crotonic, fumaric and orotic acids. Has no fumarate reductase or succinate dehydrogenase activity.[1] Publication Abstract from PubMedThe human microbiome can produce metabolites that modulate insulin signaling. Type 2 diabetes patients have increased circulating concentrations of the microbially produced histidine metabolite, imidazole propionate (ImP) and administration of ImP in mice resulted in impaired glucose tolerance. Interestingly, the fecal microbiota of the patients had increased capacity to produce ImP, which is mediated by the bacterial enzyme urocanate reductase (UrdA). Here, we describe the X-ray structures of the ligand-binding domains of UrdA in four different states, representing the structural transitions along the catalytic reaction pathway of this unexplored enzyme linked to disease in humans. The structures in combination with functional data provide key insights into the mechanism of action of UrdA that open new possibilities for drug development strategies targeting type 2 diabetes. Structural characterization of the microbial enzyme urocanate reductase mediating imidazole propionate production.,Venskutonyte R, Koh A, Stenstrom O, Khan MT, Lundqvist A, Akke M, Backhed F, Lindkvist-Petersson K Nat Commun. 2021 Mar 1;12(1):1347. doi: 10.1038/s41467-021-21548-y. PMID:33649331[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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