Light-Wavelength-Based Quantitative Control of Dihydrofolate Reductase Activity by Using a Photochromic Isostere of an Inhibitor.
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.
['Mashita|Takato|T|0000-0003-1778-000X', 'Kowada|Toshiyuki|T|0000-0002-6623-6505', 'Takahashi|Hiroto|H|', 'Matsui|Toshitaka|T|0000-0003-3865-8468', 'Mizukami|Shin|S|0000-0002-2292-8606']
D001665:Binding Sites D004926:Escherichia coli D005493:Folic Acid Antagonists D007700:Kinetics D008024:Ligands D008727:Methotrexate D008968:Molecular Conformation D013762:Tetrahydrofolate Dehydrogenase
photochromism inhibitors photopharmacology methotrexate azobenzenes enzyme catalysis