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J Biol Chem, Vol. 273, Issue 34, 21648-21657, August 21, 1998

Comparative Properties of Two Cysteine Proteinases (Gingipains R), the Products of Two Related but Individual Genes of Porphyromonas gingivalis

Jan Potempa, Jowita Mikolajczyk-Pawlinska, David Brassell^¶, Daniel Nelson^¶, Ida B. Thøgersen, Jan J. Enghild, and James Travis^¶

From the  Department of Microbiology and Immunology, Institute of Molecular Biology, Jagiellonian University, 31-120 Kraków, Poland, the  Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, and the ^¶ Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602

Proteolytic enzymes produced by Porphyromonas gingivalis are important virulence factors of this periodontopathogen. Two of these enzymes, referred to as arginine-specific cysteine proteinases (gingipains R), are the product of two related genes. Here, we describe the purification of an enzyme translated from the rgpB/rgp-2 gene (gingipain R2, RGP-2) and secreted as a single chain protein of 422 residues. The enzyme occurs in several isoforms differing in pI, molecular mass, mobility in gelatin zymography gels, and affinity to arginine-Sepharose. In comparison to the 95-kDa gingipain R1, a complex of catalytic and hemagglutinin/adhesin domains, RGP-2 showed five times lower proteolytic activity, although its activity on various P₁-arginine p-nitroanilide substrates was generally higher. Gingipains R amidolytic activity, but not general proteolytic activity, was stimulated by glycyl-glycine. However, in cases of limited proteolysis, such as the inactivation of -1-antichymotrypsin, glycyl-glycine potentiated inhibitor cleavage. In contrast, -1-proteinase inhibitor was not inactivated by gingipains R and only underwent proteolytic degradation during boiling in reducing SDS-polyacrylamide gel electrophoresis treatment buffer. Similarly, native type I collagen was completely resistant to cleavage by gingipains but readily degraded after denaturation. Together, these data explain much of the controversy regarding gingipains structure and substrate specificity and indicate that these enzymes function as P. gingivalis virulence factors by proteolysis of selected target proteins rather than random degradation of host connective tissue components.

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