The identification of proteinases of Porphyromonas gingivalis that act as virulence factors in periodontal disease has important implications in the study of host-pathogen interactions as well as in the discovery of potential therapeutic and immunoprophylactic agents. We have cloned and characterized a gene that encodes the 50-kDa cysteine proteinase gingipain or Arg-gingipain-1 (RGP-1) described previously (Chen, Z., Potempa, J., Polanowski, A., Wikstrom, M., and Travis, J. (1992) J. Biol. Chem. 267, 18896-18901). Analysis of the amino acid sequence of RGP-1 deduced from the cloned DNA sequence showed that the biosynthesis of this proteinase involves processing of a polyprotein that contains multiple adhesin molecules located at its carboxyl terminus. This finding corroborates previous evidence (Pike R., McGraw, W., Potempa, J., and Travis, J.(1994) J. Biol. Chem. 269, 406-411) that RGP-1 is closely associated with adhesin molecules, and that high molecular weight forms of the proteinase are involved in the binding of erythrocytes.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				E. Sakai, M. Naito, K. Sato, H. Hotokezaka, T. Kadowaki, A. Kamaguchi, K. Yamamoto, K. Okamoto, and K. Nakayama Construction of Recombinant Hemagglutinin Derived from the Gingipain-Encoding Gene of Porphyromonas gingivalis, Identification of Its Target Protein on Erythrocytes, and Inhibition of Hemagglutination by an Interdomain Regional Peptide J. Bacteriol., June 1, 2007; 189(11): 3977 - 3986. [Abstract] [Full Text] [PDF]

				K. Yamatake, M. Maeda, T. Kadowaki, R. Takii, T. Tsukuba, T. Ueno, E. Kominami, S. Yokota, and K. Yamamoto Role for Gingipains in Porphyromonas gingivalis Traffic to Phagolysosomes and Survival in Human Aortic Endothelial Cells Infect. Immun., May 1, 2007; 75(5): 2090 - 2100. [Abstract] [Full Text] [PDF]

				R. D. Pathirana, N. M. O'Brien-Simpson, G. C. Brammar, N. Slakeski, and E. C. Reynolds Kgp and RgpB, but Not RgpA, Are Important for Porphyromonas gingivalis Virulence in the Murine Periodontitis Model Infect. Immun., March 1, 2007; 75(3): 1436 - 1442. [Abstract] [Full Text] [PDF]

				C. A. Seers, N. Slakeski, P. D. Veith, T. Nikolof, Y.-Y. Chen, S. G. Dashper, and E. C. Reynolds The RgpB C-Terminal Domain Has a Role in Attachment of RgpB to the Outer Membrane and Belongs to a Novel C-Terminal-Domain Family Found in Porphyromonas gingivalis. J. Bacteriol., September 1, 2006; 188(17): 6376 - 6386. [Abstract] [Full Text] [PDF]

				K. Sato, E. Sakai, P. D. Veith, M. Shoji, Y. Kikuchi, H. Yukitake, N. Ohara, M. Naito, K. Okamoto, E. C. Reynolds, et al. Identification of a New Membrane-associated Protein That Influences Transport/Maturation of Gingipains and Adhesins of Porphyromonas gingivalis J. Biol. Chem., March 11, 2005; 280(10): 8668 - 8677. [Abstract] [Full Text] [PDF]

				R. Takii, T. Kadowaki, A. Baba, T. Tsukuba, and K. Yamamoto A Functional Virulence Complex Composed of Gingipains, Adhesins, and Lipopolysaccharide Shows High Affinity to Host Cells and Matrix Proteins and Escapes Recognition by Host Immune Systems Infect. Immun., February 1, 2005; 73(2): 883 - 893. [Abstract] [Full Text] [PDF]

				K.-A. Nguyen, A. A. DeCarlo, M. Paramaesvaran, C. A. Collyer, D. B. Langley, and N. Hunter Humoral Responses to Porphyromonas gingivalis Gingipain Adhesin Domains in Subjects with Chronic Periodontitis Infect. Immun., March 1, 2004; 72(3): 1374 - 1382. [Abstract] [Full Text] [PDF]

				M.-P. Savariau-Lacomme, C. Lebarbier, T. Karjalainen, A. Collignon, and C. Janoir Transcription and Analysis of Polymorphism in a Cluster of Genes Encoding Surface-Associated Proteins of Clostridium difficile J. Bacteriol., August 1, 2003; 185(15): 4461 - 4470. [Abstract] [Full Text] [PDF]

				A. Kamaguchi, T. Ohyama, E. Sakai, R. Nakamura, T. Watanabe, H. Baba, and K. Nakayama Adhesins encoded by the gingipain genes of Porphyromonas gingivalis are responsible for co-aggregation with Prevotella intermedia Microbiology, May 1, 2003; 149(5): 1257 - 1264. [Abstract] [Full Text] [PDF]

				J. Mikolajczyk, K. M. Boatright, H. R. Stennicke, T. Nazif, J. Potempa, M. Bogyo, and G. S. Salvesen Sequential Autolytic Processing Activates the Zymogen of Arg-gingipain J. Biol. Chem., March 14, 2003; 278(12): 10458 - 10464. [Abstract] [Full Text] [PDF]

				P. L. W. Yun, A. A. DeCarlo, C. Collyer, and N. Hunter Modulation of an Interleukin-12 and Gamma Interferon Synergistic Feedback Regulatory Cycle of T-Cell and Monocyte Cocultures by Porphyromonas gingivalis Lipopolysaccharide in the Absence or Presence of Cysteine Proteinases Infect. Immun., October 1, 2002; 70(10): 5695 - 5705. [Abstract] [Full Text] [PDF]

				M. Shoji, D. B. Ratnayake, Y. Shi, T. Kadowaki, K. Yamamoto, F. Yoshimura, A. Akamine, M. A. Curtis, and K. Nakayama Construction and characterization of a nonpigmented mutant of Porphyromonas gingivalis: cell surface polysaccharide as an anchorage for gingipains Microbiology, April 1, 2002; 148(4): 1183 - 1191. [Abstract] [Full Text] [PDF]

				N. A. Burgess, D. F. Kirke, P. Williams, K. Winzer, K. R. Hardie, N. L. Meyers, J. Aduse-Opoku, M. A. Curtis, and M. Camara LuxS-dependent quorum sensing in Porphyromonas gingivalis modulates protease and haemagglutinin activities but is not essential for virulence Microbiology, March 1, 2002; 148(3): 763 - 772. [Abstract] [Full Text] [PDF]

				A. P. C. A. Lima, P. C. Almeida, I. L. S. Tersariol, V. Schmitz, A. H. Schmaier, L. Juliano, I. Y. Hirata, W. Muller-Esterl, J. R. Chagas, and J. Scharfstein Heparan Sulfate Modulates Kinin Release by Trypanosoma cruzi through the Activity of Cruzipain J. Biol. Chem., February 15, 2002; 277(8): 5875 - 5881. [Abstract] [Full Text] [PDF]

				J. C. Fenno, S. Y. Lee, C. H. Bayer, and Y. Ning The opdB Locus Encodes the Trypsin-Like Peptidase Activity of Treponema denticola Infect. Immun., October 1, 2001; 69(10): 6193 - 6200. [Abstract] [Full Text] [PDF]

				T. Olczak, D. W. Dixon, and C. A. Genco Binding Specificity of the Porphyromonas gingivalis Heme and Hemoglobin Receptor HmuR, Gingipain K, and Gingipain R1 for Heme, Porphyrins, and Metalloporphyrins J. Bacteriol., October 1, 2001; 183(19): 5599 - 5608. [Abstract] [Full Text] [PDF]

				A. Sroka, M. Sztukowska, J. Potempa, J. Travis, and C. A. Genco Degradation of Host Heme Proteins by Lysine- and Arginine-Specific Cysteine Proteinases (Gingipains) of Porphyromonas gingivalis J. Bacteriol., October 1, 2001; 183(19): 5609 - 5616. [Abstract] [Full Text] [PDF]

				P. L. W. Yun, A. A. Decarlo, C. Collyer, and N. Hunter Hydrolysis of Interleukin-12 by Porphyromonas gingivalis Major Cysteine Proteinases May Affect Local Gamma Interferon Accumulation and the Th1 or Th2 T-Cell Phenotype in Periodontitis Infect. Immun., September 1, 2001; 69(9): 5650 - 5660. [Abstract] [Full Text] [PDF]

				M. Oido-Mori, R. Rezzonico, P.-L. Wang, Y. Kowashi, J.-M. Dayer, P. C. Baehni, and C. Chizzolini Porphyromonas gingivalis Gingipain-R Enhances Interleukin-8 but Decreases Gamma Interferon-Inducible Protein 10 Production by Human Gingival Fibroblasts in Response to T-Cell Contact Infect. Immun., July 1, 2001; 69(7): 4493 - 4501. [Abstract] [Full Text] [PDF]

				H. Yonezawa, K. Ishihara, and K. Okuda Arg-Gingipain A DNA Vaccine Induces Protective Immunity against Infection by Porphyromonas gingivalis in a Murine Model Infect. Immun., May 1, 2001; 69(5): 2858 - 2864. [Abstract] [Full Text] [PDF]

				T. Chen, K. Nakayama, L. Belliveau, and M. J. Duncan Porphyromonas gingivalis Gingipains and Adhesion to Epithelial Cells Infect. Immun., May 1, 2001; 69(5): 3048 - 3056. [Abstract] [Full Text] [PDF]

				K. Rice, R. Peralta, D. Bast, J. de Azavedo, and M. J. McGavin Description of Staphylococcus Serine Protease (ssp) Operon in Staphylococcus aureus and Nonpolar Inactivation of sspA-Encoded Serine Protease Infect. Immun., January 1, 2001; 69(1): 159 - 169. [Abstract] [Full Text] [PDF]

				J. Aduse-Opoku, N. N. Davies, A. Gallagher, A. Hashim, H. E. A. Evans, M. Rangarajan, J. M. Slaney, and M. A. Curtis Generation of Lys-gingipain protease activity in Porphyromonas gingivalis W50 is independent of Arg-gingipain protease activities Microbiology, August 1, 2000; 146(8): 1933 - 1940. [Abstract] [Full Text]

				N. M. O'Brien-Simpson, R. A. Paolini, and E. C. Reynolds RgpA-Kgp Peptide-Based Immunogens Provide Protection against Porphyromonas gingivalis Challenge in a Murine Lesion Model Infect. Immun., July 1, 2000; 68(7): 4055 - 4063. [Abstract] [Full Text] [PDF]

				N. M. O'Brien-Simpson, C. L. Black, P. S. Bhogal, S. M. Cleal, N. Slakeski, T. J. Higgins, and E. C. Reynolds Serum Immunoglobulin G (IgG) and IgG Subclass Responses to the RgpA-Kgp Proteinase-Adhesin Complex of Porphyromonas gingivalis in Adult Periodontitis Infect. Immun., May 1, 2000; 68(5): 2704 - 2712. [Abstract] [Full Text] [PDF]

				E. Kozarov, N. Miyashita, J. Burks, K. Cerveny, T. A. Brown, W. P. McArthur, and A. Progulske-Fox Expression and Immunogenicity of Hemagglutinin A from Porphyromonas gingivalis in an Avirulent Salmonella enterica Serovar Typhimurium Vaccine Strain Infect. Immun., February 1, 2000; 68(2): 732 - 739. [Abstract] [Full Text] [PDF]

				H. Dong, T. Chen, F. E. Dewhirst, R. D. Fleischmann, C. M. Fraser, and M. J. Duncan Genomic Loci of the Porphyromonas gingivalis Insertion Element IS1126 Infect. Immun., July 1, 1999; 67(7): 3416 - 3423. [Abstract] [Full Text] [PDF]

				Y. Shi, D. B. Ratnayake, K. Okamoto, N. Abe, K. Yamamoto, and K. Nakayama Genetic Analyses of Proteolysis, Hemoglobin Binding, and Hemagglutination of Porphyromonas gingivalis. CONSTRUCTION OF MUTANTS WITH A COMBINATION OF rgpA, rgpB, kgp, AND hagA J. Biol. Chem., June 18, 1999; 274(25): 17955 - 17960. [Abstract] [Full Text] [PDF]

				P. L. W. Yun, A. A. DeCarlo, and N. Hunter Modulation of Major Histocompatibility Complex Protein Expression by Human Gamma Interferon Mediated by Cysteine Proteinase-Adhesin Polyproteins of Porphyromonas gingivalis Infect. Immun., June 1, 1999; 67(6): 2986 - 2995. [Abstract] [Full Text] [PDF]

				J. P. Lewis and F. L. Macrina Localization of HArep-Containing Genes on the Chromosome of Porphyromonas gingivalis W83 Infect. Immun., May 1, 1999; 67(5): 2619 - 2623. [Abstract] [Full Text] [PDF]

				Y. Shibata, M. Hayakawa, H. Takiguchi, T. Shiroza, and Y. Abiko Determination and Characterization of the Hemagglutinin-associated Short Motifs Found in Porphyromonas gingivalis Multiple Gene Products J. Biol. Chem., February 19, 1999; 274(8): 5012 - 5020. [Abstract] [Full Text] [PDF]

				G. A. Barkocy-Gallagher, J. W. Foley, and M. S. Lantz Activities of the Porphyromonas gingivalis PrtP Proteinase Determined by Construction of prtP-Deficient Mutants and Expression of the Gene in Bacteroides Species J. Bacteriol., January 1, 1999; 181(1): 246 - 255. [Abstract] [Full Text]

				R. J. Lamont and H. F. Jenkinson Life Below the Gum Line: Pathogenic Mechanisms of Porphyromonas gingivalis Microbiol. Mol. Biol. Rev., December 1, 1998; 62(4): 1244 - 1263. [Abstract] [Full Text] [PDF]

				T. Kadowaki, K. Nakayama, F. Yoshimura, K. Okamoto, N. Abe, and K. Yamamoto Arg-gingipain Acts as a Major Processing Enzyme for Various Cell Surface Proteins in Porphyromonas gingivalis J. Biol. Chem., October 30, 1998; 273(44): 29072 - 29076. [Abstract] [Full Text] [PDF]

				Y. Park and R. J. Lamont Contact-Dependent Protein Secretion in Porphyromonas gingivalis Infect. Immun., October 1, 1998; 66(10): 4777 - 4782. [Abstract] [Full Text] [PDF]

				C. A. Genco, B. M. Odusanya, J. Potempa, J. Mikolajczyk-Pawlinska, and J. Travis A Peptide Domain on Gingipain R Which Confers Immunity against Porphyromonas gingivalis Infection in Mice Infect. Immun., September 1, 1998; 66(9): 4108 - 4114. [Abstract] [Full Text] [PDF]

				J. Potempa, J. Mikolajczyk-Pawlinska, D. Brassell, D. Nelson, I. B. Thogersen, J. J. Enghild, and J. Travis Comparative Properties of Two Cysteine Proteinases (Gingipains R), the Products of Two Related but Individual Genes of Porphyromonas gingivalis J. Biol. Chem., August 21, 1998; 273(34): 21648 - 21657. [Abstract] [Full Text] [PDF]

				K. Okamoto, K. Nakayama, T. Kadowaki, N. Abe, D. B. Ratnayake, and K. Yamamoto Involvement of a Lysine-specific Cysteine Proteinase in Hemoglobin Adsorption and Heme Accumulation by Porphyromonas gingivalis J. Biol. Chem., August 14, 1998; 273(33): 21225 - 21231. [Abstract] [Full Text] [PDF]

				J. P. Lewis and F. L. Macrina IS195, an Insertion Sequence-Like Element Associated with Protease Genes in Porphyromonas gingivalis Infect. Immun., July 1, 1998; 66(7): 3035 - 3042. [Abstract] [Full Text] [PDF]

				Y. Shibata, K. Kurihara, H. Takiguchi, and Y. Abiko Construction of a Functional Single-Chain Variable Fragment Antibody against Hemagglutinin from Porphyromonas gingivalis Infect. Immun., May 1, 1998; 66(5): 2207 - 2212. [Abstract] [Full Text] [PDF]

				J. Aduse-Opoku, M. Rangarajan, K. A. Young, and M. A. Curtis Maturation of the Arginine-Specific Proteases of Porphyromonas gingivalis W50 Is Dependent on a Functional prR2 Protease Gene Infect. Immun., April 1, 1998; 66(4): 1594 - 1600. [Abstract] [Full Text] [PDF]

				M. Tokuda, T. Karunakaran, M. Duncan, N. Hamada, and H. Kuramitsu Role of Arg-Gingipain A in Virulence of Porphyromonas gingivalis Infect. Immun., March 1, 1998; 66(3): 1159 - 1166. [Abstract] [Full Text] [PDF]

				E. Del Nery, M. A. Juliano, A. P. C. A. Lima, J. Scharfstein, and L. Juliano Kininogenase Activity by the Major Cysteinyl Proteinase (Cruzipain) from Trypanosoma cruzi J. Biol. Chem., October 10, 1997; 272(41): 25713 - 25718. [Abstract] [Full Text] [PDF]

				T. Imamura, J. Potempa, S. Tanase, and J. Travis Activation of Blood Coagulation Factor X by Arginine-specific Cysteine Proteinases (Gingipain-Rs) from Porphyromonas gingivalis J. Biol. Chem., June 20, 1997; 272(25): 16062 - 16067. [Abstract] [Full Text] [PDF]

				N. Pavloff, P. A. Pemberton, J. Potempa, W.-C. A. Chen, R. N. Pike, V. Prochazka, M. C. Kiefer, J. Travis, and P. J. Barr Molecular Cloning and Characterization of Porphyromonas gingivalis Lysine-specific Gingipain. A NEW MEMBER OF AN EMERGING FAMILY OF PATHOGENIC BACTERIAL CYSTEINE PROTEINASES J. Biol. Chem., January 17, 1997; 272(3): 1595 - 1600. [Abstract] [Full Text] [PDF]

				K. Nakayama, T. Kadowaki, K. Okamoto, and K. Yamamoto Construction and Characterization of Arginine-specific Cysteine Proteinase (Arg-gingipain)-deficient Mutants of Porphyromonas gingivalis J. Biol. Chem., October 6, 1995; 270(40): 23619 - 23626. [Abstract] [Full Text] [PDF]

				Y. Shi, W. Kong, and K. Nakayama Human Lactoferrin Binds and Removes the Hemoglobin Receptor Protein of the Periodontopathogen Porphyromonas gingivalis J. Biol. Chem., September 22, 2000; 275(39): 30002 - 30008. [Abstract] [Full Text] [PDF]

				T. Imamura, A. Banbula, P. J. B. Pereira, J. Travis, and J. Potempa Activation of Human Prothrombin by Arginine-specific Cysteine Proteinases (Gingipains R) from Porphyromonas gingivalis* J. Biol. Chem., May 25, 2001; 276(22): 18984 - 18991. [Abstract] [Full Text] [PDF]