Stability of plasminogen activator inhibitor‐1: role of tyrosine221

FEBS Letters

Sui, Guang-Chao¹  Wiman, Björn¹ 

[1] Department of Clinical Chemistry and Blood Coagulation, Karolinska Hospital, Karolinska Institute, S-171 76 Stockholm, Sweden

关键词: Plasminogen activator inhibitor-1;    Mutation;    Stability;   

DOI  :  10.1016/S0014-5793(98)00115-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown