Serpin‐like properties of α1‐antitrypsin Portland towards furin convertase

FEBS Letters

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