Glutathione (GSH) is a tripeptide important in preventing cellular oxidative damage. Human glutathione synthetase (GS) catalyzes the second step of GSH biosynthesis. Homodimeric human GS is negatively cooperative with respect to its L-γ-Glu-Cys substrate.  Negative cooperativity is rare and usually occurs at key metabolic branch points, and little is known about the molecular basis of negative cooperativity in hGS. Knowledge of the mechanism and reaction order of hGS is vital to understand how it contributes to the regulation of the levels of the limiting amino acid cysteine and of glutathione. In plants and prokaryotes, GS is reported to exhibit opposing random ter and ordered ter-ter reaction orders, respectively. However, little is current known about the reaction order in human GS. Using isothermal microcalorimetry (ITC) binding studies, the mechanism of action and reaction order of human GS are evaluated in order to more fully understand the molecular basis of negative cooperativity in hGS.<br/>

Human glutathione synthetase: Negative cooperativity and binding studies

2019 Spring National Meeting

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