Enzyme catalysis: the case of the prostate-specific antigen

Magda Gioia, Luigi Tomao, Diego Sbardella, Chiara Ciaccio, Grazia Raffaella Tundo, Alessandra Di Masi, Giovanni Francesco Fasciglione, Stefano Marini, Paola Cozza, Paolo Ascenzi, Massimo Coletta

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Proteases are a class of enzymes that lower the activation energy for the cleavage of the peptide bonds by polarizing the carbonyl group. The catalytic mechanism of proteases is characterized by the formation and the dissociation of a tetrahedral acyl-intermediate. The rate-limiting step in catalysis is either the acylation process (leading to the release of the newly formed -NH3+ terminal) or the subsequent deacylation step (leading to the release of the newly formed –COO terminal). As a case, the detailed kinetic analysis for the hydrolysis of the chromogenic substrate Mu-His-Ser-Ser-Lys-Leu-Gln-AMC (wherein Mu is the morpholinocarbonyl protecting group and AMC is the 7-amino-4-methylcoumarin chromophoric group) by the prostate-specific antigen (PSA) is reported here. The pH dependence of the catalytic parameters clearly indicates the existence of protonation/deprotonation processes involving (at least) two ionizing groups in the proximity of the active site. In view of the physio-pathological relevance of PSA in prostate diseases (including cancer), the detailed analysis of the catalytic parameters opens new scenarios for the design of selective inhibitors, which might influence the “in vivo” activity of this protease.

Original languageEnglish
Pages (from-to)229-237
Number of pages9
JournalRendiconti Lincei
Volume28
DOIs
Publication statusPublished - Jul 1 2017

Fingerprint

prostate-specific antigen
catalysis
Prostate-Specific Antigen
antigen
Catalysis
catalytic activity
Peptide Hydrolases
proteinases
enzyme
Enzymes
enzymes
peptide
activation energy
cleavage
Chromogenic Compounds
inhibitor
hydrolysis
cancer
acylation
Enzyme Activation

Keywords

  • Enzyme kinetics
  • Pre-steady-state kinetics
  • Prostate-specific antigen
  • PSA
  • Steady-state kinetics

ASJC Scopus subject areas

  • Environmental Science(all)
  • Agricultural and Biological Sciences(all)
  • Earth and Planetary Sciences(all)

Cite this

Gioia, M., Tomao, L., Sbardella, D., Ciaccio, C., Tundo, G. R., Di Masi, A., ... Coletta, M. (2017). Enzyme catalysis: the case of the prostate-specific antigen. Rendiconti Lincei, 28, 229-237. https://doi.org/10.1007/s12210-017-0602-6

Enzyme catalysis : the case of the prostate-specific antigen. / Gioia, Magda; Tomao, Luigi; Sbardella, Diego; Ciaccio, Chiara; Tundo, Grazia Raffaella; Di Masi, Alessandra; Fasciglione, Giovanni Francesco; Marini, Stefano; Cozza, Paola; Ascenzi, Paolo; Coletta, Massimo.

In: Rendiconti Lincei, Vol. 28, 01.07.2017, p. 229-237.

Research output: Contribution to journalArticle

Gioia, M, Tomao, L, Sbardella, D, Ciaccio, C, Tundo, GR, Di Masi, A, Fasciglione, GF, Marini, S, Cozza, P, Ascenzi, P & Coletta, M 2017, 'Enzyme catalysis: the case of the prostate-specific antigen', Rendiconti Lincei, vol. 28, pp. 229-237. https://doi.org/10.1007/s12210-017-0602-6
Gioia M, Tomao L, Sbardella D, Ciaccio C, Tundo GR, Di Masi A et al. Enzyme catalysis: the case of the prostate-specific antigen. Rendiconti Lincei. 2017 Jul 1;28:229-237. https://doi.org/10.1007/s12210-017-0602-6
Gioia, Magda ; Tomao, Luigi ; Sbardella, Diego ; Ciaccio, Chiara ; Tundo, Grazia Raffaella ; Di Masi, Alessandra ; Fasciglione, Giovanni Francesco ; Marini, Stefano ; Cozza, Paola ; Ascenzi, Paolo ; Coletta, Massimo. / Enzyme catalysis : the case of the prostate-specific antigen. In: Rendiconti Lincei. 2017 ; Vol. 28. pp. 229-237.
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