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. (c) 2006 Elsevier B.V. All rights reserved.

Caselli, A., Casolaro, M., Rinaldi, F., Manao, G., Camici, G., Giachetti, E. (2007). Kinetic mechanism of the Zn-dependent aryl-phosphatase activity of myo-inositol-1-phosphatase. BIOPHYSICAL CHEMISTRY, 125(2-3), 435-443 [10.1016/j.bpc.2006.10.004].

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

Casolaro, Mario;
2007-01-01

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. (c) 2006 Elsevier B.V. All rights reserved.
2007
Caselli, A., Casolaro, M., Rinaldi, F., Manao, G., Camici, G., Giachetti, E. (2007). Kinetic mechanism of the Zn-dependent aryl-phosphatase activity of myo-inositol-1-phosphatase. BIOPHYSICAL CHEMISTRY, 125(2-3), 435-443 [10.1016/j.bpc.2006.10.004].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/9134
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