Structure and kinetics of gamma glutamyl transferases from bacillus species

Abstract

Gamma Glutamyl Transferases (GGT) are highly conserved enzymes that act on substrates of the form Glu-γCO-NHR. The enzyme removes the terminal glutamate and transfers it to water (hydrolase activity) or an acceptor compound with a free amine group (transferase activity). Under physiological conditions, mammalian GGTs appear to act on glutathione and contribute to its homeostatic level. Human GGT has been implicated in a number of pathological conditions like diabetes, neurodegenerative diseases, induction of apoptosis and cancer. The physiological function of plant and bacterial GGTs is not known unambiguously. The homologue constitutes a virulence factor in Helicobater pylori and Bacillus anthracis. Structurally, GGT belongs to the superfamily of N-terminal nucleophile (Ntn) hydrolases. The enzyme is produced as an inactive single chain precursor which undergoes self-activation to form an active heterodimer. The side chain hydroxyl group of the Thr residue that occurs at the newly exposed N terminus functions as the catalytic nucleophile. B. subtilis GGT is an extracellular enzyme composed of two subunits weighing 40 and 20KDa. The enzyme is speculated to support nitrogen nutrition during adverse conditions.