The involvement of tryptase, the trypsin-like serine proteinase of mast cell granules, in many (patho)physiological conditions is now recognized. In vitro this enzyme is known to act as a potent growth factor for fibroblasts and epithelial cells. Moreover, a role in inflammatory diseases and in dermatological disorders characterized by increased cell turnover has been suggested for this protease. In an attempt to understand the molecular basis of tryptase activity, we have investigated the interaction in vitro between bovine tryptase and histones. Here we show that tryptase cleaves histone H2A at a specific site (Arg20-Ala21), resulting in the removal of the N-terminal flexible fragment of the molecule, Furthermore, we demonstrate that the H2A major fragment (H2A*, 109 residues) generated by hydrolysis and lacking the N-terminal domain, is a noncompetitive, reversible and highly specific inhibitor (K-i = 29 nM) of tryptase enzymatic activity. H2A* is able to inhibit the hydrolysis of a small substrate as well as the cleavage of fibronectin, a high-molecular-weight substrate of tryptase. (C) 1997 Academic Press.

Fiorucci, L., Erba, F., Ascoli, F. (1997). Histone-tryptase interaction: H2A N-terminal tail removal and inhibitory activity. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 347(2), 229-234 [10.1006/abbi.1997.0338].

Histone-tryptase interaction: H2A N-terminal tail removal and inhibitory activity

Fiorucci, L;Erba, F;
1997-11-15

Abstract

The involvement of tryptase, the trypsin-like serine proteinase of mast cell granules, in many (patho)physiological conditions is now recognized. In vitro this enzyme is known to act as a potent growth factor for fibroblasts and epithelial cells. Moreover, a role in inflammatory diseases and in dermatological disorders characterized by increased cell turnover has been suggested for this protease. In an attempt to understand the molecular basis of tryptase activity, we have investigated the interaction in vitro between bovine tryptase and histones. Here we show that tryptase cleaves histone H2A at a specific site (Arg20-Ala21), resulting in the removal of the N-terminal flexible fragment of the molecule, Furthermore, we demonstrate that the H2A major fragment (H2A*, 109 residues) generated by hydrolysis and lacking the N-terminal domain, is a noncompetitive, reversible and highly specific inhibitor (K-i = 29 nM) of tryptase enzymatic activity. H2A* is able to inhibit the hydrolysis of a small substrate as well as the cleavage of fibronectin, a high-molecular-weight substrate of tryptase. (C) 1997 Academic Press.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10
English
histone H2A
tryptase
inhibitor
fibronectin
Animals
Cattle
Chymases
Dose-Response Relationship, Drug
Histones
Hydrolysis
Kinetics
Liver
Peptide Fragments
Serine Endopeptidases
Serine Proteinase Inhibitors
Tryptases
Fiorucci, L., Erba, F., Ascoli, F. (1997). Histone-tryptase interaction: H2A N-terminal tail removal and inhibitory activity. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 347(2), 229-234 [10.1006/abbi.1997.0338].
Fiorucci, L; Erba, F; Ascoli, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/258256
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