Mammalian tissues contain two low M(r) phosphotyrosine protein phosphatase isoforms (type-I and type-2) that differ in the 40-73 amino-acid sequence. Only one isoform (type-2) is strongly inhibited by pyridoxal 5'-phosphate, whereas the other is poorly inhibited by this compound. The mechanism of pyridoxal 5'-phosphate inhibition of the bovine liver enzyme (a type-2 isoform) has been studied by kinetic methods using a series of pyridoxal 5'-phosphate analogues. These studies indicate that pyridoxal 5'-phosphate interacts with the enzyme in both the phosphate and aldehyde groups. Active site-directed mutagenesis has been used to investigate the sites of pyridoxal 5'-phosphate binding. Our results indicate that Cys-17, essential for enzyme activity, interacts with the phosphate moiety of pyridoxal 5'-phosphate. On the other hand, Cys-12, which is also involved in the catalytic mechanism, does not participate in pyridoxal 5'-phosphate binding.

The role of Cys-17 in the pyridoxal 5'-phosphate inhibition of the bovine liver low M(r) phosphotyrosine protein phosphatase / P. CIRRI; P. CHIARUGI ; G. CAMICI ; G. MANAO ; L. PAZZAGLI ; A. CASELLI ; I. BARGHINI ; G. CAPPUGI ; G. RAUGEI ; G. RAMPONI. - In: BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE. - ISSN 0925-4439. - STAMPA. - 1161:(1993), pp. 216-222. [10.1016/0167-4838(93)90216-E]

The role of Cys-17 in the pyridoxal 5'-phosphate inhibition of the bovine liver low M(r) phosphotyrosine protein phosphatase.

CIRRI, PAOLO;CHIARUGI, PAOLA;CAMICI, GUIDO;MANAO, GIAMPAOLO;PAZZAGLI, LUIGIA;CASELLI, ANNA;CAPPUGI, GIANNI;RAUGEI, GIOVANNI;RAMPONI, GIAMPIETRO
1993

Abstract

Mammalian tissues contain two low M(r) phosphotyrosine protein phosphatase isoforms (type-I and type-2) that differ in the 40-73 amino-acid sequence. Only one isoform (type-2) is strongly inhibited by pyridoxal 5'-phosphate, whereas the other is poorly inhibited by this compound. The mechanism of pyridoxal 5'-phosphate inhibition of the bovine liver enzyme (a type-2 isoform) has been studied by kinetic methods using a series of pyridoxal 5'-phosphate analogues. These studies indicate that pyridoxal 5'-phosphate interacts with the enzyme in both the phosphate and aldehyde groups. Active site-directed mutagenesis has been used to investigate the sites of pyridoxal 5'-phosphate binding. Our results indicate that Cys-17, essential for enzyme activity, interacts with the phosphate moiety of pyridoxal 5'-phosphate. On the other hand, Cys-12, which is also involved in the catalytic mechanism, does not participate in pyridoxal 5'-phosphate binding.
1993
1161
216
222
P. CIRRI; P. CHIARUGI ; G. CAMICI ; G. MANAO ; L. PAZZAGLI ; A. CASELLI ; I. BARGHINI ; G. CAPPUGI ; G. RAUGEI ; G. RAMPONI
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/205839
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