Reversible optical control of F1 Fo -ATP synthase using photoswitchable inhibitors

FEBS Lett. 2018 Feb;592(3):343-355. doi: 10.1002/1873-3468.12958. Epub 2018 Feb 1.

Abstract

F1 Fo -ATP synthase is one of the best studied macromolecular machines in nature. It can be inhibited by a range of small molecules, which include the polyphenols, resveratrol and piceatannol. Here, we introduce Photoswitchable Inhibitors of ATP Synthase, termed PIAS, which were synthetically derived from these polyphenols. They can be used to reversibly control the enzymatic activity of purified yeast Yarrowia lipolyticaATP synthase by light. Our experiments indicate that the PIAS bind to the same site in the ATP synthase F1 complex as the polyphenols in their trans form, but they do not bind in their cis form. The PIAS could be useful tools for the optical precision control of ATP synthase in a variety of biochemical and biotechnological applications.

Keywords: Yarrowia lipolytica F1Fo-ATP synthase; photopharmacology.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Binding Sites
  • Crystallography, X-Ray
  • Fungal Proteins / chemistry
  • Fungal Proteins / metabolism
  • Hydrolysis
  • Mitochondrial Proton-Translocating ATPases / antagonists & inhibitors*
  • Mitochondrial Proton-Translocating ATPases / chemistry*
  • Models, Molecular
  • Photochemical Processes
  • Polyphenols / chemical synthesis*
  • Polyphenols / chemistry
  • Polyphenols / pharmacology
  • Protein Binding
  • Protein Conformation
  • Yarrowia / enzymology*

Substances

  • Fungal Proteins
  • Polyphenols
  • Adenosine Triphosphate
  • F1F0-ATP synthase
  • Mitochondrial Proton-Translocating ATPases

Associated data

  • PDB/2JIZ
  • PDB/2jiz
  • PDB/5fl7