Glutathione S-transferase (GST) (GST)

Glutathione S-transferases (GSTs) are a superfamily of Phase II metabolic enzymes essential for cellular detoxification and the maintenance of redox homeostasis. They catalyze the nucleophilic attack of reduced glutathione (GSH) on electrophilic centers of various endogenous and exogenous compounds, including environmental toxins and therapeutic drugs, rendering them more water-soluble for excretion (UniProt P09211). In clinical oncology, GSTs, particularly the Pi class (GSTP1), are frequently overexpressed in tumors, where they contribute to chemotherapy resistance by neutralizing antineoplastic agents or inhibiting pro-apoptotic signaling pathways like JNK (PubMed 15829718). Beyond their role as targets for overcoming drug resistance, GSTs are frequently identified as off-targets in drug discovery due to their broad substrate binding pockets and high abundance in the liver and other tissues. Computational or "in silico" modeling often flags GSTs as potential interactors to predict metabolic stability or potential toxicity arising from the depletion of cellular glutathione levels (PubChem). Understanding GST interactions is therefore vital for optimizing drug efficacy and minimizing adverse reactions related to oxidative stress.

Other names

Glutathione transferaseLigandinGSTP1GSTM1GSTA1GSTT1

GSTs catalyze the conjugation of reduced glutathione (GSH) to electrophilic substrates, facilitating their detoxification and subsequent excretion via the mercapturic acid pathway. They also act as non-enzymatic binding proteins (ligandins) and modulate signaling pathways, such as the JNK pathway, to regulate apoptosis.