Structural characterization of the microbial enzyme urocanate reductase mediating imidazole propionate production

Raminta Venskutonytė, Ara Koh, Olof Stenström, Muhammad Tanweer Khan, Annika Lundqvist, Mikael Akke, Fredrik Bäckhed and Karin Lindkvist-Petersson ()
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Raminta Venskutonytė: BMC C13, Lund University
Ara Koh: University of Gothenburg
Olof Stenström: Lund University
Muhammad Tanweer Khan: University of Gothenburg
Annika Lundqvist: University of Gothenburg
Mikael Akke: Lund University
Fredrik Bäckhed: University of Gothenburg
Karin Lindkvist-Petersson: BMC C13, Lund University

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract The 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.

Date: 2021
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DOI: 10.1038/s41467-021-21548-y

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