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

A. M. Caccuri, G. Ricci, A. Desideri, M. Buffa, R. Fruttero, A. Gasco, P. Ascenzi

Research output: Contribution to journalArticle

11 Citations (Scopus)

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°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-nitrobenzoic 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).

Original languageEnglish
Pages (from-to)819-829
Number of pages11
JournalBiochemistry and Molecular Biology International
Volume32
Issue number5
Publication statusPublished - 1994

Fingerprint

Glutathione S-Transferase pi
Placenta
Nitrobenzoates
Dithiothreitol
Enzyme Inhibitors
Enzymes
Glutathione Transferase
Reaction products
Sulfhydryl Compounds
Disulfides
Dimers
Rate constants
Catalyst activity
Catalytic Domain
calvatic acid
Anti-Bacterial Agents
Recovery
Molecules
Experiments

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Molecular Biology

Cite this

Caccuri, A. M., Ricci, G., Desideri, A., Buffa, M., Fruttero, R., Gasco, A., & Ascenzi, P. (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, A. M.; Ricci, G.; Desideri, A.; Buffa, M.; Fruttero, R.; Gasco, A.; Ascenzi, P.

In: Biochemistry and Molecular Biology International, Vol. 32, No. 5, 1994, p. 819-829.

Research output: Contribution to journalArticle

Caccuri, AM, Ricci, G, Desideri, A, Buffa, M, Fruttero, R, Gasco, A & Ascenzi, P 1994, 'Inhibition of human placenta glutathione transferase P1-1 by calvatic acid', Biochemistry and Molecular Biology International, vol. 32, no. 5, pp. 819-829.
Caccuri AM, Ricci G, Desideri A, Buffa M, Fruttero R, Gasco A et al. Inhibition of human placenta glutathione transferase P1-1 by calvatic acid. Biochemistry and Molecular Biology International. 1994;32(5):819-829.
Caccuri, A. M. ; Ricci, G. ; Desideri, A. ; Buffa, M. ; Fruttero, R. ; Gasco, A. ; Ascenzi, P. / Inhibition of human placenta glutathione transferase P1-1 by calvatic acid. In: Biochemistry and Molecular Biology International. 1994 ; Vol. 32, No. 5. pp. 819-829.
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