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

Journal Article · · Protein Science
DOI:https://doi.org/10.1002/pro.3444· OSTI ID:1491841
 [1];  [1];  [1];  [1];  [2]
  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)
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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.
Research Organization:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE; USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1491841
Alternate ID(s):
OSTI ID: 1459683
Journal Information:
Protein Science, Journal Name: Protein Science Journal Issue: 8 Vol. 27; ISSN 0961-8368
Publisher:
The Protein SocietyCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (4)

Predicting associations among drugs, targets and diseases by tensor decomposition for drug repositioning journal December 2019
Crosstalk between gut microbiota and antidiabetic drug action journal March 2019
Identification of α-glucosidase inhibitors from cyclocarya paliurus tea leaves using UF-UPLC-Q/TOF-MS/MS and molecular docking journal January 2019
Clinical and genetic predictors of diabetes drug’s response journal August 2019

Figures / Tables (7)

Table 1(p. 22)table Table 1
Table 2(p. 23)table Table 2
Figure 1(p. 24)figure Figure 1
Figure 2(p. 25)figure Figure 2
Figure 3(p. 27)figure Figure 3
Figure 4(p. 29)figure Figure 4
Figure 5(p. 30)figure Figure 5

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
acarbose
anti-diabetic drug
human gut microbiome
miglitol
substrate/inhibitor selection
voglibose
α-glucosidase
α-glucosidase inhibitor