Modeling the Catalytic Cycle of Glutathione Peroxidase by Nuclear Magnetic Resonance Spectroscopic Analysis of Selenocysteine Selenenic Acids

Abstract

Although selenocysteine selenenic acids (Sec–SeOHs) have been recognized as key intermediates in the catalytic cycle of glutathione peroxidase (GPx), examples of the direct observation of Sec–SeOH in either protein or small-molecule systems have remained elusive so far, mostly due to their instability. Here, we report the first direct spectroscopic (1H and 77Se NMR) evidence for the formation of Sec–SeOH in small-molecule selenocysteine and selenopeptide model systems with a cradle-type protective group. The catalytic cycle of GPx was investigated using NMR-observable Sec–SeOH models. All the hitherto proposed chemical processes, i.e., not only those of the canonical catalytic cycle but also those involved in the bypass mechanism, including the intramolecular cyclization of Sec–SeOH to the corresponding five-membered ring selenenyl amide, were examined in a stepwise manner.

Observation and Nursing of Adverse Reactions in Severe Patients with Enhanced MRI

“…High quality nursing service is the key to ensure the successful and safe completion of MRI scanning and ensure the image quality [ 6 , 7 ]. Masuda, R. and others pointed out that effective nursing intervention for patients undergoing MRI Dynamic enhancement scanning can alleviate their negative emotions before the examination and maintain a peaceful state of mind during the examination, so as to help them successfully complete the examination [ 8 ]. Clinical research shows that effective nursing intervention for patients undergoing MRI Dynamic enhancement scanning can improve their negative emotions before examination and make them complete the examination smoothly.…”

Selenium-Catalyzed Reduction of Hydroperoxides in Chemistry and Biology

“…This latter product, like all selenenic derivatives, is experimentally elusive and has not been detected. Only when the selenium is protected by cradle-shaped molecular structure, selenenic acids could be synthetized [14,15].…”

“…It may sound risky to invoke an extremely unstable intermediate without analytical proof. Yet more recently, Masuda et al [14] have provided NMR evidence that a cradle-protected selenocysteine can be oxidized to a selenenic acid and that the latter, like in glutathione peroxidases, readily reacts with thiols and less fast with NH-groups, while deselenylation is even less favoured.…”

Rational design of allosteric switchable catalysts

“…Recently, versatile molecular scaffolds were utilized to afford exceptional examples aiming at natural enzymes' expertise: facilitating the formation of enzymesubstrate complex and reducing the activation energy barrier of catalytic reactions. Essential knowledge and critical factors (e.g., hydrogen bonds, electrostatic potential, van der Waals' forces, coordination bonds) that govern the enzyme activity have been explored by studying different models such as small organic molecules, [14][15][16][17][18][19][20] polymers, [21][22][23][24][25][26][27][28][29] supramolecular complexes, [30][31][32][33][34][35][36][37] natural proteins, [38][39][40][41][42][43][44] and protein assemblies. [45][46][47][48][49][50][51][52] These multidisciplinary works have spawned many successful bioinspired enzymes, some of which even showed high efficiencies comparable to their natural counterparts.…”