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

doi:10.1002/pro.3444

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:

Tan, Kemin ^[1]; Tesar, Christine ^[1]; Wilton, Rosemarie ^[1]; Jedrzejczak, Robert P. ^[1]; Joachimiak, Andrzej ^[2]

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:: 2018-05-15

Research Org.:: Argonne National Lab. (ANL), Argonne, IL (United States)

Sponsoring Org.:: USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)

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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Works referenced in this record:

Cell-wall carbohydrates and their modification as a resource for biofuels
journal, May 2008

Pauly, Markus; Keegstra, Kenneth
The Plant Journal, Vol. 54, Issue 4, p. 559-568
DOI: 10.1111/j.1365-313X.2008.03463.x

The Path Forward for Biofuels and Biomaterials
journal, January 2006

Ragauskas, Arthur J.; Williams, Charlotte K.; Davison, Brian H.
Science, Vol. 311, Issue 5760, p. 484-489
DOI: 10.1126/science.1114736

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

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Citation Formats

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The Path Forward for Biofuels and Biomaterials journal, January 2006

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The Path Forward for Biofuels and Biomaterials
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