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 language | English |
|---|---|
| Pages (from-to) | 959-972 |
| Number of pages | 14 |
| Journal | Journal of Biomolecular Structure and Dynamics |
| Volume | 7 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1990 |
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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
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 journal › Article
}
TY - JOUR
T1 - Thermodynamic modeling of internal equilibria involved in the activation of trypsinogen
AU - Coletta, Massimo
AU - Ascenzi, Paolo
AU - Bravin, Laura
AU - Amiconi, Gino
AU - Bolognesi, Martino
AU - Guarneri, Mario
AU - Menegatti, Enea
PY - 1990
Y1 - 1990
N2 - 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).
AB - 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).
KW - (β-)trypsin(ogen) inhibitors
KW - Bovine trypsinogen
KW - Bovine β-trypsin
KW - Thermodynamic modeling of trypsinogen activation
KW - Trypsinogen activating dipeptides
KW - Trypsinogen activation
UR - http://www.scopus.com/inward/record.url?scp=0025213399&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025213399&partnerID=8YFLogxK
U2 - 10.1080/07391102.1990.10508535
DO - 10.1080/07391102.1990.10508535
M3 - Article
C2 - 2310525
AN - SCOPUS:0025213399
VL - 7
SP - 959
EP - 972
JO - Journal of Biomolecular Structure and Dynamics
JF - Journal of Biomolecular Structure and Dynamics
SN - 0739-1102
IS - 4
ER -