Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 101, Issue -, Pages 153-164Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2017.03.087
Keywords
E. coli F-1 F-0 ATP synthase; Olive phenolics; Tyrosol; Hydroxytyrosol; Dihydroxyphenylglycol; Oleuropein; Enzyme inhibition
Funding
- National Institutes of Health [GM085771]
- A.T. Still University-Kirksville College of Osteopathic Medicine Biomedical Science Graduate Program [850-611]
- Kirksville College of Osteopathic Medicine
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The naturally occurring olive phenolics tyrosol, hydroxytyrosol, dihydroxyphenylglycol (DHPG), and oleuropein are known to have antioxidant, antitumor, and antibacterial properties. In the current study, we examined whether the antimicrobial properties of tyrosol, hydroxytyrosol, DHPG, and oleuropein were linked to the inhibition of bacterial ATP synthase. Tyrosol, hydroxytyrosol, DHPG; and oleuropein inhibited Escherichia coil wild-type and mutant membrane-bound F1Fa ATP synthase to variable degrees. The growth properties of wild-type, null, and mutant strains in presence of above olive phenolics were also abrogated to variable degrees on limiting glucose and succinate. Tyrosol and oleuropein synergistically inhibited the wild-type enzyme. Comparative wild-type and mutant F-1 F-0 ATP synthase inhibitory profiles suggested that alpha Arg-283 is an important residue and olive phenolics bind at the polyphenol binding pocket of ATP synthase. Growth patterns of wild-type, null, and mutant strains in the presence of tyrosol, hydroxytyrosol, DHPG, and oleuropein also hint at the possibility of additional molecular targets. Our results demonstrated that ATP synthase can be used as a molecular target and the antimicrobial properties of olive phenolics in general and tyrosol in particular can be linked to the binding and inhibition of bacterial ATP synthase. (C) 2017 Elsevier B.V. All rights reserved.
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