Interaction of antidiabetic α-glucosidase inhibitors and gut bacteria α-glucosidase
Abstract
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 antidiabetic α‐glucosidase inhibitors voglibose, miglitol, and acarbose and supporting binding data. The in vitro binding of these antidiabetic drugs to Ro ‐αG1 suggests the potential for unintended in vivo crossreaction of the α‐glucosidase inhibitors to bacterial α‐glucosidases that are present in gut microorganism communities. Moreover, analysis of these drug‐bound enzyme structures could benefit further antidiabetic 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 Laboratory (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. https://doi.org/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. https://doi.org/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 = {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 antidiabetic α‐glucosidase inhibitors voglibose, miglitol, and acarbose and supporting binding data. The in vitro binding of these antidiabetic drugs to Ro ‐αG1 suggests the potential for unintended in vivo crossreaction of the α‐glucosidase inhibitors to bacterial α‐glucosidases that are present in gut microorganism communities. Moreover, analysis of these drug‐bound enzyme structures could benefit further antidiabetic drug development.},
doi = {10.1002/pro.3444},
journal = {Protein Science},
number = 8,
volume = 27,
place = {United States},
year = {Tue May 15 00:00:00 EDT 2018},
month = {Tue May 15 00:00:00 EDT 2018}
}
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