title: Inhibition of human placenta glutathione transferase P1-1 by calvatic acid.
abstract: The inhibition mechanism of the dimeric human placenta glutathione transferase (GST P1-1) by the antibiotic p-carboxyphenylazoxycyanide (calvatic acid) has been investigated at pH 7.0 and 30.0 degrees C. Experiments performed at different calvatic acid/GST P1-1 molar ratios indicate that one mole of calvatic acid inactivates one mole of the homodimeric enzyme molecule, containing two catalytically equivalent active sites. The apparent second order rate constant for GST P1-1 inactivation is 2.4 +/- 0.3 M-1 s-1. The recovery of all the 5,5'-dithio-bis(2-nitro-benzoic acid)-titratable thiol groups as well as the original catalytic activity of GST P1-1 after treatment of the inhibited enzyme with dithiothreitol indicates that two disulfide bridges per dimer, likely between Cys47 and Cys101, have been formed during the reaction with calvatic acid. To the best of the authors knowledge, calvatic acid represents a unique case of enzyme inhibitor acting also throughout its reaction product(s).
authors.affiliation: Dipartimento di Biologia, Universita' di Roma Tor Vergata, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Caccuri
authors.forename: G
authors.initials: G
authors.lastname: Ricci
authors.forename: A
authors.initials: A
authors.lastname: Desideri
authors.forename: M
authors.initials: M
authors.lastname: Buffa
authors.forename: R
authors.initials: R
authors.lastname: Fruttero
authors.forename: A
authors.initials: A
authors.lastname: Gasco
authors.forename: P
authors.initials: P
authors.lastname: Ascenzi
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology; D004220:Disulfides / Q000737:chemistry; D005260:Female; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D009570:Nitriles / Q000494:pharmacology; D010084:Oxidation-Reduction; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy
chemical_list: D000900:Anti-Bacterial Agents; D001565:Benzoates; D004220:Disulfides; D009570:Nitriles; C010057:calvatic acid; D005982:Glutathione Transferase