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Proteolytic inactivation of human α 1 antitrypsin by human stromelysin
Author(s) -
Winyard Paul G.,
Zhang Zhi,
Chidwick Keith,
Blake David R.,
Carrell Robin W.,
Murphy Gillian
Publication year - 1991
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 - 10.1016/0014-5793(91)80258-5
Subject(s) - elastase , neutrophil elastase , cleavage (geology) , chemistry , metalloproteinase , microbiology and biotechnology , serine protease , peptide , biochemistry , protease , serine , peptide sequence , proteolysis , gel electrophoresis , serine proteinase inhibitors , matrix metalloproteinase , enzyme , biology , inflammation , immunology , gene , paleontology , fracture (geology)
α 1 Antitrypsin (α 1 AT) is the main physiological inhibitor of neutrophil elastase, a serine protease which has been implicated in tissue degradation at inflammatory sites. We report here that the connective tissue metalloproteinase, stromelysin, cleaved α 1 AT (54 kDa), producing fragments of approximately 50 kDa and 4 kDa, as shown by gel electrophoresis. The cleavage of α 1 AT was accompanied by inactivation of its elastase inhibitory capacity. Isolation of the 4 kDa fragment by reversed‐phase HPLC, followed by N‐terminal amino acid sequencing, demonstrated that the cleavage of α 1 AT occurred at the Pro 357 ‐Met 358 (P 2 –P 1 ) peptide bond, one peptide bond to the N‐terminal side of the inhibitory site. We suggest that stromelysin may potentiate the activity of neutrophil elastase by proteolytically inactivating α 1 AT.