Stability of plasminogen activator inhibitor-1: role of tyrosine221.
Using site-directed mutagenesis, changes of Tyr221 in plasminogen activator inhibitor-1 (PAI-1) have provided mutants with normal activity, but with increased stability. At physiological conditions, the transition of the PAI-1 mutants Tyr221His and Tyr221Ser to the latent form was significantly prolonged (half-lives 14.8 and 4.1 h, respectively) as compared to wild-type PAI-1 (2.0 h). Their half-lives, especially for the Tyr221Ser mutant, were even more prolonged in the presence of vitronectin (23.8 and 53.7 h, respectively). While wild-type PAI-1 was more stable at lower pH, the PAI-1 mutants Tyr221His and Tyr221Ser had stability optima at about pH 6.5, but displayed shorter half-lives at pH 5.5.
Sui
G C
GC
Department of Clinical Chemistry and Blood Coagulation, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Wiman
B
B
D004795:Enzyme Stability / Q000235:genetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D013696:Temperature; D014443:Tyrosine / Q000502:physiology*; D019096:Vitronectin / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; D019096:Vitronectin; D014443:Tyrosine; D010960:Plasminogen Activators