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).

Caccuri, A.m., Ricci, G., Desideri, A., Buffa, M., Fruttero, R., Gasco, A., et al. (1994). Inhibition of human placenta glutathione transferase P1-1 by calvatic acid. BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL, 32(5), 819-829.

Inhibition of human placenta glutathione transferase P1-1 by calvatic acid

CACCURI, ANNA MARIA;RICCI, GIORGIO;DESIDERI, ALESSANDRO;
1994-04-01

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).
apr-1994
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Con Impact Factor ISI
oxidation-reduction; nitriles; anti-bacterial agents; benzoates; placenta; humans; glutathione transferase; disulfides; female; pregnancy
Caccuri, A.m., Ricci, G., Desideri, A., Buffa, M., Fruttero, R., Gasco, A., et al. (1994). Inhibition of human placenta glutathione transferase P1-1 by calvatic acid. BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL, 32(5), 819-829.
Caccuri, Am; Ricci, G; Desideri, A; Buffa, M; Fruttero, R; Gasco, A; Ascenzi, P
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/69113
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