Temperature adaptation of glutathione S-transferase P1-1 - A case for homotropic regulation of substrate binding

Human glutathione S-transferase P1-1 (GST P1-1) is a homodimeric enzyme exp ressed in several organs as well as in the upper layers of epidermis, playi ng a role against carcinogenic and toxic compounds. A sophisticated mechani sm of temperature adaptation has been developed by this enzyme. In fact, ab ove 35 degrees C, glutathione (GSH) binding to GST P1-1 displays positive c ooperativity, whereas negative cooperativity occurs below 25 degrees C. Thi s binding mechanism minimizes changes of GSH affinity for GST P1-1 because of temperature fluctuation. This is a likely advantage for epithelial skin cells, which are naturally exposed to temperature variation and, incidental ly, to carcinogenic compounds, always needing efficient detoxifying systems . As a whole, GST P1-1 represents the first enzyme which displays a tempera ture-dependent homotropic regulation of substrate (e.g. GSH) binding.