Rational Design of an Organometallic Glutathione Transferase Inhibitor

摘要

Glutathione transferases (EC 2.5.1.18; GSTs) catalyze the nucleophilic attack by reduced glutathione (GSH) on non-polar compounds with electrophilic centers, acting on a range of exogenous substances (e.g. carcinogens and cancer chemo-therapeutic agents) as well as endogenous compounds, forming part of a coordinated defense strategy to remove GSH conjugates from the cell. In mammals, there are two major families of soluble GSTs, located in the cytosol and mitochondria. These enzymes are dimeric proteins that can be grouped into at least eight gene-independent classes on the basis of their primary structure. Their three-dimensional structures do not differ significantly despite low sequence homology, yet the different classes display a broad range of functions.