A novel arginine-specific cysteine proteinase, termed 'argingipain,' was purified from culture supernatants of Porphyromonas gingivalis, an anaerobe commonly associated with progressive periodontal disease, by conventional chromatographic techniques. The purified enzyme was found to be composed of a single polypeptide of M(r) ~44,000. Analysis of the enzymatic properties revealed several distinctive features for this enzyme. The proteolytic activity is absolutely thiol-dependent, but the enzyme also has in part the characteristics of both metallo and serine endopeptidases, as shown by the inhibition of activity by metal chelators, chymostatin, and the chloromethyl ketones of tosyl-L-lysine and tosyl-L-phenylalanine. However, internal protease inhibitors, such as cystatins, tissue inhibitor of metalloproteinases, and α1-antichymotrypsin, have no effects on the activity, suggesting its evasion from normal host defense systems in vivo. Despite its narrow specificity for synthetic substrates containing Arg in the P1 site and hydrophobic amino acids in the P2 or P3 sites, the enzyme extensively degrades collagens (types I and IV) and immunoglobulin G. Most important, the enzyme has the ability to disrupt the functions of polymorphonuclear leukocytes, as shown by its inhibitory effect on the generation of active oxygen species from the activated cells. Further, the enzyme is found to be produced by all of the species of P. gingivalis examined, but not by other bacteria. These results suggests that argingipain plays a key role as a major virulence factor from P. gingivalis in the development of periodontal disease via the direct destruction of periodontal tissue components and the disruption of normal host defense mechanisms.
|Number of pages||8|
|Journal||Journal of Biological Chemistry|
|Publication status||Published - Jan 1 1994|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology