STABILITY OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 - ROLE OF TYROSINE(221)

Using site-directed mutagenesis, changes of Tyr(221) in plasminogen ac tivator inhibitor-1 (PAI-1) have provided mutants with normal activity , but with increased stability. At physiological conditions, the trans ition of the PAI-1 mutants Tyr(221)His and Tyr(221)Ser to the latent f orm was significantly prolonged (half-lives 14.8 and 4.1 h, respective ly) as compared to wild-type PAI-1 (2.0 h), Their half-lives, especial ly for the Tyr(221)Ser mutant, were even more prolonged in the presenc e of vitronectin (23.8 and 53.7 h, respectively). While wild-type PAI- 1 was more stable at lower pH, the PAI-1 mutants Tyr(221)His and Tyr(2 21)Ser had stability optima at about pH 6.5, but displayed shorter hal f-lives at pH 5.5. (C) 1998 Federation of European Biochemical Societi es.