title: Interstitial collagenase (matrix metalloproteinase-1) expresses serpinase activity.
abstract: Human endothelial cells treated with either interleukin-1 beta, tumor necrosis factor-alpha, or phorbol myristate acetate secreted a metalloproteinase that hydrolyzed and inactivated the two major serine proteinase inhibitors (Serpins) found in plasma, alpha 1-proteinase inhibitor and alpha 1-antichymotrypsin. Surprisingly, the responsible metalloproteinase was identified as human interstitial collagenase (matrix metalloproteinase-1), an enzyme whose only known physiologic substrate has heretofore been believed to be the extracellular matrix molecule, collagen. The metalloproteinase inactivated the Serpins by cleaving peptide bonds at sites unrelated to those hydrolyzed in collagenous macromolecules. NH2-terminal sequence analysis localized the cleavage sites in the Serpins to regions near their respective reactive site centers at three distinct peptide bonds on the amino-terminal side of bulky, hydrophobic residues. Together, these data indicate that matrix metalloproteinase-1 displays an expanded substrate repertoire that supports the existence of a new interface between connective tissue turnover and Serpin function.
authors.affiliation: Department of Internal Medicine, Simpson Memorial Research Institute, University of Michigan, Ann Arbor 48109.
authors.forename: P E
authors.initials: PE
authors.lastname: Desrochers
authors.forename: J J
authors.initials: JJ
authors.lastname: Jeffrey
authors.forename: S J
authors.initials: SJ
authors.lastname: Weiss
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000201:enzymology*; D006801:Humans; D020781:Matrix Metalloproteinase 1; D003012:Microbial Collagenase / Q000378:metabolism*; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D015843:Serpins / Q000378:metabolism*; D013379:Substrate Specificity; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
chemical_list: D015843:Serpins; D000514:alpha 1-Antichymotrypsin; D000515:alpha 1-Antitrypsin; D003012:Microbial Collagenase; D020781:Matrix Metalloproteinase 1