Nitric oxide causes inactivation of the low molecular weight phosphotyrosine protein phosphatase.

ABSTRACT: The low M, phosphotyrosine protein phosphatase PTPase) and Yersinia enterocolitica PTPase are inacti- ated by nitric oxide-generating compounds. Inorganic hosphate, a competitive inhibitor, protects the en- ymes from inactivation, suggesting that the action of O is directed to the active sites. Low M, PTPase from ovine liver lost two out of eight thiol groups present i he molecule during the inactivation with sodium nitro- russide and with other NO-producing compounds. mass spectrometric analyses of tryptic fragments of the nzyme, performed after chemical modification of the O-unreacted thiol groups, demonstrated that NO aused the oxidation of Cys-12 and Cys-17 to form an S-S ond. A similar reaction was described previously for he reaction of NO with h”methyh-aspartate receptor. he NO-inactivated low M, PTPase was reactivated by reating the inactive enzyme with thiol-containing re- gents. Since all members of the PTPase family have the ame reaction mechanism and possess a conserved ac- ve site motif that contains an essential cysteine resi- ue, the findings on low M, and Yersinia PTPases are otentially interesting for all PTPases, an enzyme class hat is involved in a number of important biological rocesses.