title: Nitric oxide causes inactivation of the low molecular weight phosphotyrosine protein phosphatase.
abstract: The low M(r) phosphotyrosine protein phosphatase (PTPase) and Yersinia enterocolitica PTPase are inactivated by nitric oxide-generating compounds. Inorganic phosphate, a competitive inhibitor, protects the enzymes from inactivation, suggesting that the action of NO is directed to the active sites. Low M(r) PTPase from bovine liver lost two out of eight thiol groups present in the molecule during the inactivation with sodium nitroprusside and with other NO-producing compounds. The mass spectrometric analyses of tryptic fragments of the enzyme, performed after chemical modification of the NO-unreacted thiol groups, demonstrated that NO caused the oxidation of Cys-12 and Cys-17 to form an S-S bond. A similar reaction was described previously for the reaction of NO with N-methyl-D-aspartate receptor. The NO-inactivated low M(r) PTPase was reactivated by treating the inactive enzyme with thiol-containing reagents. Since all members of the PTPase family have the same reaction mechanism and possess a conserved active site motif that contains an essential cysteine residue, the findings on low M(r) and Yersinia PTPases are potentially interesting for all PTPases, an enzyme class that is involved in a number of important biological processes.
authors.affiliation: Dipartimento di Scienze Biochimiche, Università di Firenze, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Caselli
authors.forename: G
authors.initials: G
authors.lastname: Camici
authors.forename: G
authors.initials: G
authors.lastname: Manao
authors.forename: G
authors.initials: G
authors.lastname: Moneti
authors.forename: L
authors.initials: L
authors.lastname: Pazzagli
authors.forename: G
authors.initials: G
authors.lastname: Cappugi
authors.forename: G
authors.initials: G
authors.lastname: Ramponi
mesh_terms: D000595:Amino Acid Sequence; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009569:Nitric Oxide / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D015008:Yersinia enterocolitica / Q000201:enzymology
chemical_list: D009569:Nitric Oxide; D017027:Protein Tyrosine Phosphatases