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Light‐Wavelength‐Based Quantitative Control of Dihydrofolate Reductase Activity by Using a Photochromic Isostere of an Inhibitor
Author(s) -
Mashita Takato,
Kowada Toshiyuki,
Takahashi Hiroto,
Matsui Toshitaka,
Mizukami Shin
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800816
Subject(s) - dihydrofolate reductase , photoisomerization , chemistry , biomolecule , ligand (biochemistry) , photochromism , optogenetics , enzyme , combinatorial chemistry , biophysics , photochemistry , biochemistry , isomerization , biology , catalysis , receptor , neuroscience
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.