Myo-inositol-1-phosphatase (EC 3.1.3.25) is able to hydrolyze myo-inositol-1-phosphate in the presence of Mg2+ ions at neutral pH, and also p-nitrophenyl phosphate in the presence of Zn2+-ions at acidic pH. This enzyme plays a role in phosphatidylinositol cell signalling and is a putative target of lithium therapy in manic depression. We elucidate here the kinetic mechanism of the Zn-dependent activity of myo-inositol-1-phosphatase. As part of this analysis it was necessary to determine the basicity constants of p-nitrophenyl phosphate and the stability constant of its metal-complex in the presence of zinc chloride. We find that the Zn-dependent reaction may be described either by a rapid-equilibrium random mechanism or an ordered steady-state mechanism in which the substrate binds to the free enzyme prior to the metal ion. In both models the Zn-substrate complex acts as a high affinity inhibitor, yielding a dead-end species through its binding to the enzyme-Zn-substrate in rapid-equilibrium or to the enzyme-phosphate complexes in a steady-state model. Phosphate is a competitive inhibitor of the enzyme with respect to the substrate and an uncompetitive inhibitor with respect to zinc ions.

Kinetic mechanism of the Zn-dependent aryl-phosphatase activity of myo-inositol-1-phosphatase / A. Caselli; M. Casolaro; F. Ranaldi; G. Manao; G. Camici; E. Giachetti. - In: BIOPHYSICAL CHEMISTRY. - ISSN 0301-4622. - STAMPA. - 125:(2007), pp. 435-443. [10.1016/j.bpc.2006.10.004]

Kinetic mechanism of the Zn-dependent aryl-phosphatase activity of myo-inositol-1-phosphatase

CASELLI, ANNA;RANALDI, FRANCESCO;MANAO, GIAMPAOLO;CAMICI, GUIDO;GIACHETTI, EUGENIO
2007

Abstract

Myo-inositol-1-phosphatase (EC 3.1.3.25) is able to hydrolyze myo-inositol-1-phosphate in the presence of Mg2+ ions at neutral pH, and also p-nitrophenyl phosphate in the presence of Zn2+-ions at acidic pH. This enzyme plays a role in phosphatidylinositol cell signalling and is a putative target of lithium therapy in manic depression. We elucidate here the kinetic mechanism of the Zn-dependent activity of myo-inositol-1-phosphatase. As part of this analysis it was necessary to determine the basicity constants of p-nitrophenyl phosphate and the stability constant of its metal-complex in the presence of zinc chloride. We find that the Zn-dependent reaction may be described either by a rapid-equilibrium random mechanism or an ordered steady-state mechanism in which the substrate binds to the free enzyme prior to the metal ion. In both models the Zn-substrate complex acts as a high affinity inhibitor, yielding a dead-end species through its binding to the enzyme-Zn-substrate in rapid-equilibrium or to the enzyme-phosphate complexes in a steady-state model. Phosphate is a competitive inhibitor of the enzyme with respect to the substrate and an uncompetitive inhibitor with respect to zinc ions.
2007
125
435
443
A. Caselli; M. Casolaro; F. Ranaldi; G. Manao; G. Camici; E. Giachetti
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/312927
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