1. Proteolytic inactivation of human α1 antitrypsin by human stromelysin
- Author
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Keith Chidwick, David R. Blake, Robin W. Carrell, Zhi Zhang, Gillian Murphy, and Paul G. Winyard
- Subjects
Neutrophils ,Molecular Sequence Data ,Biophysics ,Connective tissue ,Biochemistry ,Neutrophil elastase ,Structural Biology ,Genetics ,medicine ,Humans ,Peptide bond ,Amino Acid Sequence ,Enzyme Inhibitors ,Molecular Biology ,Chromatography, High Pressure Liquid ,Serine protease ,chemistry.chemical_classification ,Gel electrophoresis ,Inflammation ,Metalloproteinase ,Pancreatic Elastase ,biology ,Chemistry ,Hydrolysis ,Elastase ,Stromelysin ,Metalloendopeptidases ,Cell Biology ,Proteolytic inactivation ,Amino acid ,medicine.anatomical_structure ,alpha 1-Antitrypsin ,biology.protein ,α1Antitrypsin ,Electrophoresis, Polyacrylamide Gel ,Matrix Metalloproteinase 3 ,Human - Abstract
alpha 1 Antitrypsin (alpha 1AT) 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 alpha 1AT (54 kDa), producing fragments of approximately 50 kDa and 4 kDa, as shown by gel electrophoresis. The cleavage of alpha 1AT 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 alpha 1AT occurred at the Pro357-Met358 (P2-P1) 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 alpha 1AT.
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