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

Venskutonytė, Raminta LU ; Koh, Ara ; Stenström, Olof LU ; Khan, Muhammad Tanweer ; Lundqvist, Annika ; Akke, Mikael LU ; Bäckhed, Fredrik and Lindkvist-Petersson, Karin LU (2021) In Nature Communications 12(1). p.1347-1347
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... (More)

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.

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organization
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type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
12
issue
1
pages
1347 - 1347
publisher
Nature Publishing Group
external identifiers
  • scopus:85102223471
  • pmid:33649331
ISSN
2041-1723
DOI
10.1038/s41467-021-21548-y
language
English
LU publication?
yes
id
a7f2cf89-a0c9-4ccc-8803-2300ac609241
date added to LUP
2021-03-24 14:29:45
date last changed
2021-04-27 01:11:24
@article{a7f2cf89-a0c9-4ccc-8803-2300ac609241,
  abstract     = {<p>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.</p>},
  author       = {Venskutonytė, Raminta and Koh, Ara and Stenström, Olof and Khan, Muhammad Tanweer and Lundqvist, Annika and Akke, Mikael and Bäckhed, Fredrik and Lindkvist-Petersson, Karin},
  issn         = {2041-1723},
  language     = {eng},
  number       = {1},
  pages        = {1347--1347},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Structural characterization of the microbial enzyme urocanate reductase mediating imidazole propionate production},
  url          = {http://dx.doi.org/10.1038/s41467-021-21548-y},
  doi          = {10.1038/s41467-021-21548-y},
  volume       = {12},
  year         = {2021},
}