title: Temperature adaptation of glutathione S-transferase P1-1. A case for homotropic regulation of substrate binding.
abstract: Human glutathione S-transferase P1-1 (GST P1-1) is a homodimeric enzyme expressed in several organs as well as in the upper layers of epidermis, playing a role against carcinogenic and toxic compounds. A sophisticated mechanism of temperature adaptation has been developed by this enzyme. In fact, above 35 degrees C, glutathione (GSH) binding to GST P1-1 displays positive cooperativity, whereas negative cooperativity occurs below 25 degrees C. This 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, incidentally, to carcinogenic compounds, always needing efficient detoxifying systems. As a whole, GST P1-1 represents the first enzyme which displays a temperature-dependent homotropic regulation of substrate (e.g. GSH) binding.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, I-00133 Rome, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Caccuri
authors.forename: G
authors.initials: G
authors.lastname: Antonini
authors.forename: P
authors.initials: P
authors.lastname: Ascenzi
authors.forename: M
authors.initials: M
authors.lastname: Nicotra
authors.forename: M
authors.initials: M
authors.lastname: Nuccetelli
authors.forename: A P
authors.initials: AP
authors.lastname: Mazzetti
authors.forename: G
authors.initials: G
authors.lastname: Federici
authors.forename: M
authors.initials: M
authors.lastname: Lo Bello
authors.forename: G
authors.initials: G
authors.lastname: Ricci
mesh_terms: D000222:Adaptation, Physiological; D019943:Amino Acid Substitution; D005978:Glutathione / Q000378:metabolism; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology*; D008956:Models, Chemical; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D014443:Tyrosine / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D014443:Tyrosine; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D005978:Glutathione