Degradation of elastin by a cysteine proteinase from Staphylococcus aureus.
Staphylococcus aureus is known to produce three very active extracellular proteinases. One of these enzymes, a cysteine proteinase, after purification to homogeneity was found to degrade insoluble bovine lung elastin at a rate comparable to human neutrophil elastase. This enzyme had no detectable activity against a range of synthetic substrates normally utilized by elastase, chymotrypsin, or trypsin-like proteinases. However, it did hydrolyze the synthetic substrate carbobenzoxy-phenylalanyl-leucyl-glutamyl-p-nitroanilide (Km = 0.5 mM, kcat = 0.16 s-1). The proteolytic activity of the cysteine proteinase was rapidly and efficiently inhibited by alpha 2-macroglobulin and also by the cysteine-specific inhibitor rat T-kininogen (Ki = 5.2 X 10(-7) M). Human kininogens, however, did not inhibit. Human plasma apparently contains other inhibitors of this enzyme, since plasma depleted of alpha 2-macroglobulin retained significant inhibitory capacity. The elastolytic activity of this S. aureus proteinase and its lack of control by human kininogens or cystatin C may explain some of the connective tissue destruction seen in bacterial infections due to this and related organisms such as may occur in septicemia, septic arthritis, and otitis.
Institute of Molecular Biology, Jagiellonian University, Cracow, Poland.
J
J
Potempa
A
A
Dubin
G
G
Korzus
J
J
Travis
D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004549:Elastin / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007704:Kininogens / Q000494:pharmacology; D008744:Methylamines / Q000494:pharmacology; D051381:Rats; D012697:Serine Endopeptidases / Q000378:metabolism; D013211:Staphylococcus aureus / Q000201:enzymology*
D007704:Kininogens; D008744:Methylamines; D004549:Elastin; C027451:methylamine; D012697:Serine Endopeptidases; C028344:glutamyl endopeptidase; D003546:Cysteine Endopeptidases