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

• Published in: FEBS letters Vol. 426; no. 1; pp. 41 - 46
• Main Authors: Dufour, Erick K, Denault, Jean-Bernard, Hopkins, Paul C.R, Leduc, Richard
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 10.04.1998
• Subjects: AT, α1-antitrypsin; Da, dalton; Furin; htAT-PDX, histidine-tagged α1-antitrypsin Portland; IPTG, isopropyl-β-d-thiogalactopyranoside; MCA, 4-methylcoumaryl-7-amide; Mechanism-based inhibition; PAGE, polyacrylamide gel electrophoresis; Protease inhibitor; RSL, reactive site loop; Serpin; Serpin, serine protease inhibitor; Subtilase; α 1-Antitrypsin; α1-Antitrypsin; Mechanism-based inhibition; IPTG, isopropyl-β- d-thiogalactopyranoside; α 1-Antitrypsin; htAT-PDX, histidine-tagged α 1-antitrypsin Portland; Serpin, serine protease inhibitor; Da, dalton; Serpin; Subtilase; PAGE, polyacrylamide gel electrophoresis; RSL, reactive site loop; Furin; AT, α 1-antitrypsin; MCA, 4-methylcoumaryl-7-amide; Protease inhibitor
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(98)00307-X

Recent studies have demonstrated that a serpin variant, α 1-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 1.5×10 6 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.