Thermodynamic modeling of internal equilibria involved in the activation of trypsinogen

Massimo Coletta, Paolo Ascenzi, Laura Bravin, Gino Amiconi, Martino Bolognesi, Mario Guarneri, Enea Menegatti

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The effect of activating dipeptides, sequentially homologous to the Ile 16-Vall 17 N-terminus of bovine β-trypsin (β-trypsin), on equilibria involved in the binding of strong ligands (i.e., n-butylamine, the bovine basic pancreatic trypsin inhibitor (Kunitz-type inhibitor; BPTI) and the porcine pancreatic secretory trypsin inhibitor (Kazal-type inhibitor, type I; PSH)) to bovine trypsinogen (trypsinogen) was investigated at pH 5.5 (I = 0.1 M) and T = 21.0 ± 0.5°C; under the same experimental conditions, thermodynamics for the binding of strong ligands to β-trypsin was also obtained. The equilibria involved in the binding of activating dipeptides and/or inhibitors to β-trypsin and to its zymogen are described according to an induced-fit formalism, taking into account ligand-linked interactions) between different functional and structural domains of the (pro)enzyme possibly involved in the trypsinogen-to-β-trypsin activation pathway. The analysis of data is focussed on parameters describing interactions between the so-called Ile-Val pocket (where the Ilel6-Vall7 N-terminus of β-trypsin or activating dipeptides bind) and the primary and/or secondary recognition subsite(s) (where strong ligands associate) present in the (pro)enzyme. Such an analysis allows to dissect the contributions due to the primary recognition subsite, where small mono-functional ligands (e.g., n-butylamine) bind, from those of the secondary subsite(s), which are additional recognition clefts for macromolecular inhibitors (e.g., BPTI and PSTI).

Original languageEnglish
Pages (from-to)959-972
Number of pages14
JournalJournal of Biomolecular Structure and Dynamics
Volume7
Issue number4
DOIs
Publication statusPublished - 1990

Fingerprint

Trypsinogen
Thermodynamics
Trypsin
Dipeptides
Ligands
Aprotinin
isoleucylvaline
Kazal Pancreatic Trypsin Inhibitor
Enzyme Precursors
Trypsin Inhibitors
Enzymes
Swine

Keywords

  • (β-)trypsin(ogen) inhibitors
  • Bovine trypsinogen
  • Bovine β-trypsin
  • Thermodynamic modeling of trypsinogen activation
  • Trypsinogen activating dipeptides
  • Trypsinogen activation

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Coletta, M., Ascenzi, P., Bravin, L., Amiconi, G., Bolognesi, M., Guarneri, M., & Menegatti, E. (1990). Thermodynamic modeling of internal equilibria involved in the activation of trypsinogen. Journal of Biomolecular Structure and Dynamics, 7(4), 959-972. https://doi.org/10.1080/07391102.1990.10508535

Thermodynamic modeling of internal equilibria involved in the activation of trypsinogen. / Coletta, Massimo; Ascenzi, Paolo; Bravin, Laura; Amiconi, Gino; Bolognesi, Martino; Guarneri, Mario; Menegatti, Enea.

In: Journal of Biomolecular Structure and Dynamics, Vol. 7, No. 4, 1990, p. 959-972.

Research output: Contribution to journalArticle

Coletta, M, Ascenzi, P, Bravin, L, Amiconi, G, Bolognesi, M, Guarneri, M & Menegatti, E 1990, 'Thermodynamic modeling of internal equilibria involved in the activation of trypsinogen', Journal of Biomolecular Structure and Dynamics, vol. 7, no. 4, pp. 959-972. https://doi.org/10.1080/07391102.1990.10508535
Coletta, Massimo ; Ascenzi, Paolo ; Bravin, Laura ; Amiconi, Gino ; Bolognesi, Martino ; Guarneri, Mario ; Menegatti, Enea. / Thermodynamic modeling of internal equilibria involved in the activation of trypsinogen. In: Journal of Biomolecular Structure and Dynamics. 1990 ; Vol. 7, No. 4. pp. 959-972.
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