Affiliation:
1. Molecular Signaling & Drug Discovery Laboratory, Department of Biochemistry, Central University of Punjab, Bathinda, 151401,
Punjab, India
Abstract
Background:
In bacteria, peptide deformylase (PDF), a metalloenzyme, removes N-formyl methionine from a nascent protein, which is a critical step in the protein maturation process. The enzyme is ubiquitously present in bacteria and possesses therapeutic target potential. Acarbose, an FDA-approved antidiabetic
drug, is an alpha-glucosidase inhibitor of microbial origin. Clinical studies indicate that acarbose administration
in humans can alter gut microbiota. As per the best of our knowledge, the antibacterial potential of acarbose has
not been reported.
Objective:
The present study aimed to check the binding ability of acarbose to the catalytic site of E. coli PDF
and assess its in vitro antibacterial activity.
Methods:
Molecular docking, molecular dynamic (MD) simulation, and MM-PBSA experiments were performed to study the binding potential of the catalytic site, and a disc diffusion assay was also employed to assess the antibacterial potential of acarbose.
Results:
Acarbose was found to form a hydrogen bond and interact with the metal ion present at the catalytic
site. The test compound showed a better docking score in comparison to the standard inhibitor of PDF. MD
simulation results showed energetically stable acarbose-PDF complex formation in terms of RMSD, RMSF,
Rg, SASA, and hydrogen bond formation throughout the simulation period compared to the actinonin-PDF
complex. Furthermore, MM-PBSA calculations showed better binding free energy (∆G) of acarbose PDF than
the actinonin-PDF complex. Moreover, acarbose showed in vitro antibacterial activity.
Conclusion:
Acarbose forms conformational and thermodynamically stable interaction with the E. coli peptide
deformylase catalytic site. Results of the present work necessitate in-depth antimicrobial potential studies on the
effect of acarbose on drug resistance and nonresistant bacteria.
Funder
DST-SERB, Department of Science and Technology, India
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology
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