Inhibition of protein tyrosine phosphatases by low-molecular-weight S-nitrosothiols and S-nitrosylated human serum albumin

The homogeneous recombinant mammalian protein tyrosine phosphatase 1B (PTP1 B) and Yersinia protein tyrosine phosphatase (PTPase) are inactivated by a series of low-molecular-weight S-nitrosothiols. These compounds exhibited d ifferent inhibitory activities in a time- and concentration-dependent manne r with second-order rate constants (k (inact)/K-I) ranging from 37 to 113 M -1 min(-1) against mammalian PTP1B and from 66 to 613 M-1 min(-1) against Y ersinia PTPase. Furthermore, the inactivation of Yersinia PTPase by S-nitro sylated protein:S-nitroso human serum albumin was investigated. Both single -S-nitrosylated and poly-S-nitrosylated human serum albumin show good inhib itory ability to Yersinia PTPase. The second-order rate constants are 472 a nd 1188 M-1 min(-1), respectively. This result indicates a possibility that S-nitrosylated albumin in vivo may function as an inhibitor for a variety of cysteine-dependent enzymes. (C) 2000 Academic Press.