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Serpin‐like properties of α1‐antitrypsin Portland towards furin convertase
Author(s) -
Dufour Erick K,
Denault Jean-Bernard,
Hopkins Paul C.R,
Leduc Richard
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)00307-x
Subject(s) - furin , serpin , proteases , serine protease , trypsin , serine , chemistry , enzyme , biochemistry , protease , proprotein convertase , microbiology and biotechnology , biology , gene , lipoprotein , ldl receptor , cholesterol
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.