FEBS Letters | |
Serpin‐like properties of α1‐antitrypsin Portland towards furin convertase | |
Dufour, Erick K2  Leduc, Richard2  Hopkins, Paul C.R1  Denault, Jean-Bernard2  | |
[1] Gladstone Institute of Cardiovascular Disease, P.O. Box 419100, San Francisco, CA 94141, USA;Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Que. J1H 5N4, Canada | |
关键词: α1-Antitrypsin; Serpin; Protease inhibitor; Furin; Subtilase; Mechanism-based inhibition; Serpin; serine protease inhibitor; RSL; reactive site loop; AT; α1-antitrypsin; htAT-PDX; histidine-tagged α1-antitrypsin Portland; Da; dalton; PAGE; polyacrylamide gel electrophoresis; MCA; 4-methylcoumaryl-7-amide; IPTG; isopropyl-β-d-thiogalactopyranoside; | |
DOI : 10.1016/S0014-5793(98)00307-X | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
Recent studies have demonstrated that a serpin variant, α1-antitrypsin Portland (AT-PDX), can inhibit the mammalian convertase furin. Here, we examine the mechanism by which this inhibition takes place. We find that furin, which does not belong to the trypsin-like serine protease family, the usual targets of serpins, forms an SDS-heat denaturation-resistant complex with AT-PDX both in vitro and in vivo. AT-PDX inhibited furin with an association rate constant (k ass) of 1.5×106 M−1 s−1 which is similar to k ass values reported for serpins with trypsin-like enzymes. These results illustrate that AT can be modified to act essentially as a suicide inhibitor of furin, an enzyme of the subtilase superfamily of serine proteases.
【 授权许可】
Unknown
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO201912020305800ZK.pdf | 237KB | download |