Matrilysin is much more efficient than other matrix metalloproteinases in the proteolytic inactivation of alpha 1-antitrypsin

Biochem Biophys Res Commun. 1994 Oct 28;204(2):613-20. doi: 10.1006/bbrc.1994.2503.


alpha 1-antitrypsin, the primary physiologic inhibitor of human leukocyte elastase, is proteolytically inactivated by several matrix metalloproteinases including interstitial collagenase, stromelysin and 92 kDa gelatinase. In this report, we describe the catalytic effects of matrilysin, a recently identified metalloproteinase, upon alpha 1-antitrypsin. Matrilysin was found to be approximately 30-fold more effective than 92kDa gelatinase, 70-fold more effective than collagenase, and 180-fold more effective than stromelysin. Cleavage of alpha 1-antitrypsin by matrilysin produced two fragments of approximately 50 kDa and 4 kDa. The single cleavage occurred at the Phe352-Leu353 peptide bond, a locus within alpha 1-antitrypsin's active-site loop. These results suggest that apart from its activity against extracellular matrix, matrilysin provides a mechanism for the regulation of leukocyte elastase activity through its capacity to degrade alpha 1-AT.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Humans
  • Hydrolysis
  • Kinetics
  • Matrix Metalloproteinase 7
  • Metalloendopeptidases / metabolism*
  • Molecular Sequence Data
  • alpha 1-Antitrypsin / metabolism*


  • alpha 1-Antitrypsin
  • Metalloendopeptidases
  • Matrix Metalloproteinase 7