Model compounds for the active site selenocysteine of glutathione peroxidase: A 77Se NMR study

Abstract

AbstractTo test the feasibility of using 77Se NMR to distinguish between different proposed mechanisms of action of the selenoenzyme glutathione peroxidase, model compounds containing the proposed selenium moieties have been synthesized and their 77Se NMR spectra recorded. It was found that the difference in chemical shift between the two proposed resting states, selenol or selenenic acid, is approximately 1300 ppm. For the next step, oxidation by hydrogen peroxide, a much smaller difference of about 100 ppm was found between selenenic and seleninic acid species. The products of the second reaction step, selenide sulfide vs selenoxide sulfide, differed in chemical shift by about 470 ppm. It was concluded that, for two of the three states of the enzyme, 77Se NMR could, in principle, be used unambiguously to distinguish between the two proposed mechanisms.