Light-Wavelength-Based Quantitative Control of Dihydrofolate Reductase Activity by Using a Photochromic Isostere of an Inhibitor

Chembiochem. 2019 Jun 3;20(11):1382-1386. doi: 10.1002/cbic.201800816. Epub 2019 Apr 3.

Abstract

Photopharmacology has attracted research attention as a new tool for achieving optical control of biomolecules, following the methods of caged compounds and optogenetics. We have developed an efficient photopharmacological inhibitor-azoMTX-for Escherichia coli dihydrofolate reductase (eDHFR) by replacing some atoms of the original ligand, methotrexate, to achieve photoisomerization properties. This fine molecular design enabled quick structural conversion between the active "bent" Z isomer of azoMTX and the inactive "extended" E isomer, and this property afforded quantitative control over the enzyme activity, depending on the wavelength of irradiating light applied. Real-time photoreversible control over enzyme activity was also achieved.

Keywords: azobenzenes; enzyme catalysis; inhibitors; methotrexate; photochromism; photopharmacology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Escherichia coli / metabolism
  • Folic Acid Antagonists / chemistry*
  • Kinetics
  • Ligands
  • Methotrexate / analogs & derivatives*
  • Molecular Conformation
  • Tetrahydrofolate Dehydrogenase / chemistry*

Substances

  • Folic Acid Antagonists
  • Ligands
  • Tetrahydrofolate Dehydrogenase
  • Methotrexate