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Stability of plasminogen activator inhibitor‐1: role of tyrosine 221
Author(s) -
Sui Guang-Chao,
Wiman Björn
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00115-x
Subject(s) - mutant , vitronectin , plasminogen activator , chemistry , wild type , tyrosine , plasminogen activator inhibitor 1 , site directed mutagenesis , mutagenesis , biochemistry , microbiology and biotechnology , biology , endocrinology , gene , receptor , integrin
Using site‐directed mutagenesis, changes of Tyr 221 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 Tyr 221 His and Tyr 221 Ser 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 Tyr 221 Ser 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 Tyr 221 His and Tyr 221 Ser had stability optima at about pH 6.5, but displayed shorter half‐lives at pH 5.5.