Capturing the Catalytic Proton of Dihydrofolate Reductase: Implications for General Acid-Base Catalysis.

ABSTRACT: Acid-base catalysis, which involves one or more proton transfer reactions, is a chemical mechanism commonly employed by many enzymes. The molecular basis for catalysis is often derived from structures determined at the optimal pH for enzyme activity. However, direct observation of protons from experimental structures is quite difficult; thus, a complete mechanistic description for most enzymes remains lacking. Dihydrofolate reductase (DHFR) exemplifies general acid-base catalysis, requiring hydride transfer and protonation of its substrate, DHF, to form the product, tetrahydrofolate (THF). Previous X-ray and neutron crystal structures coupled with theoretical calculations have proposed that solvent mediates the protonation step. However, visualization of a proton transfer has been elusive.

SUBMITTER: Wan Q 

PROVIDER: S-EPMC8154319 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature