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

Takato Mashita, Toshiyuki Kowada, Hiroto Takahashi, Toshitaka Matsui, Shin Mizukami

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1382-1386
Number of pages5
JournalChemBioChem
Volume20
Issue number11
DOIs
Publication statusPublished - 2019 Jun 3

Keywords

  • azobenzenes
  • enzyme catalysis
  • inhibitors
  • methotrexate
  • photochromism
  • photopharmacology

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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