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Title: Interaction of antidiabetic α-glucosidase inhibitors and gut bacteria α-glucosidase

Abstract

Carbohydrate hydrolyzing α-glucosidases are commonly found in microorganisms present in the human intestine microbiome. We have previously reported crystal structures of an α-glucosidase from the human gut bacterium Blaubia (Ruminococcus) obeum (Ro-αG1) and its substrate preference/specificity switch. This novel member of the GH31 family is a structural homolog of human intestinal maltase-glucoamylase (MGAM) and sucrase–isomaltase (SI) with a highly conserved active site that is predicted to be common in Ro-αG1 homologs among other species that colonize the human gut. In this report, we present structures of Ro-αG1 in complex with the anti-diabetic α-glucosidase inhibitors voglibose, miglitol and acarbose and supporting binding data. The in vitro binding of these anti-diabetic drugs to Ro-αG1 suggests the potential for unintended in vivo cross-reaction of the α-glucosidase inhibitors to bacterial α-glucosidases that are present in gut microorganism communities. As a result, analysis of these drug-bound enzyme structures could benefit further anti-diabetic drug development.

Authors:
 [1];  [1];  [1];  [1];  [2]
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  1. Argonne National Lab. (ANL), Argonne, IL (United States)
  2. Argonne National Lab. (ANL), Argonne, IL (United States); Univ. of Chicago, Chicago, IL (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1491841
Alternate Identifier(s):
OSTI ID: 1459683
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Accepted Manuscript
Journal Name:
Protein Science
Additional Journal Information:
Journal Volume: 27; Journal Issue: 8; Journal ID: ISSN 0961-8368
Publisher:
The Protein Society
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; acarbose; anti-diabetic drug; human gut microbiome; miglitol; substrate/inhibitor selection; voglibose; α-glucosidase; α-glucosidase inhibitor

Citation Formats

Tan, Kemin, Tesar, Christine, Wilton, Rosemarie, Jedrzejczak, Robert P., and Joachimiak, Andrzej. Interaction of antidiabetic α-glucosidase inhibitors and gut bacteria α-glucosidase. United States: N. p., 2018. Web. doi:10.1002/pro.3444.
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Tan, Kemin, Tesar, Christine, Wilton, Rosemarie, Jedrzejczak, Robert P., & Joachimiak, Andrzej. Interaction of antidiabetic α-glucosidase inhibitors and gut bacteria α-glucosidase. United States. doi:10.1002/pro.3444.
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Tan, Kemin, Tesar, Christine, Wilton, Rosemarie, Jedrzejczak, Robert P., and Joachimiak, Andrzej. Tue . "Interaction of antidiabetic α-glucosidase inhibitors and gut bacteria α-glucosidase". United States. doi:10.1002/pro.3444. https://www.osti.gov/servlets/purl/1491841.
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@article{osti_1491841,
title = {Interaction of antidiabetic α-glucosidase inhibitors and gut bacteria α-glucosidase},
author = {Tan, Kemin and Tesar, Christine and Wilton, Rosemarie and Jedrzejczak, Robert P. and Joachimiak, Andrzej},
abstractNote = {Carbohydrate hydrolyzing α-glucosidases are commonly found in microorganisms present in the human intestine microbiome. We have previously reported crystal structures of an α-glucosidase from the human gut bacterium Blaubia (Ruminococcus) obeum (Ro-αG1) and its substrate preference/specificity switch. This novel member of the GH31 family is a structural homolog of human intestinal maltase-glucoamylase (MGAM) and sucrase–isomaltase (SI) with a highly conserved active site that is predicted to be common in Ro-αG1 homologs among other species that colonize the human gut. In this report, we present structures of Ro-αG1 in complex with the anti-diabetic α-glucosidase inhibitors voglibose, miglitol and acarbose and supporting binding data. The in vitro binding of these anti-diabetic drugs to Ro-αG1 suggests the potential for unintended in vivo cross-reaction of the α-glucosidase inhibitors to bacterial α-glucosidases that are present in gut microorganism communities. As a result, analysis of these drug-bound enzyme structures could benefit further anti-diabetic drug development.},
doi = {10.1002/pro.3444},
journal = {Protein Science},
number = 8,
volume = 27,
place = {United States},
year = {2018},
month = {5}
}
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DOI:  10.1002/pro.3444
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Cited by: 3 works
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Table 1 Table 1: Crystallographic statistics
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    Clinical and genetic predictors of diabetes drug’s response
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