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:
-
- Argonne National Lab. (ANL), Argonne, IL (United States)
- 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.
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.
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.
@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}
}
Web of Science
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