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, Karin Lindkvist-Petersson

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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.

Originalspråkengelska
Sidor (från-till)1347
TidskriftNature Communications
Volym12
Nummer1
DOI
StatusPublished - 2021

Ämnesklassifikation (UKÄ)

  • Cell- och molekylärbiologi

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