Gingipains, a group of arginine or lysine specific cysteine proteinases (also known as RgpA, RgpB and Kgp), have been recognized as major virulence factors in Porphyromonas gingivalis. This bacterium is one of a handful of pathogens that cause chronic periodontitis. Gingipains are involved in adherence to and colonization of epithelial cells, hemagglutination and hemolysis of erythrocytes, disruption and manipulation of the inflammatory response, and the degradation of host proteins and tissues. RgpA and Kgp are multi-domain proteins composed of catalytic domains and hemagglutinin/adhesin (HA) regions. The structure of the HA regions have previously been defined by a gingipain domain structure hypothesis which is a set of putative domain boundaries derived from the sequences of fragments of these proteins extracted from the cell surface. However, multiple sequence alignments and hidden Markov models predict an alternative domain architecture for the HA regions of gingipains. In this alternate model, two or three repeats of the socalled “cleaved adhesion” domains (and one other undefined domain in some strains) are the modules which constitute the substructure of the HA regions. Recombinant forms of these putative cleaved adhesin domains are indeed stable folded protein modules and recently determined crystal structures support the hypothesis of a modular organisation of the HA region. Based on the observed K2 and K3 structures as well as multiple sequence alignments, it is proposed that all the cleaved adhesin domains in gingipains will share the same β-sandwich jelly roll fold. The new domain model of the structure for gingipains and the Hag proteins of P. gingivalis will guide future functional studies of these virulence factors.
1. R.C. Williams 1990 Periodontal disease N Engl J Med 322 373–382.
2. D.F. Kinane 2001 Causation and pathogenesis of periodontal disease Periodontol 2000 25 8–20.
3. T.F. Flemmig 1999 Periodontitis Ann Periodontol 4 32–38.
4. J. Lindhe R. Ranney I. Lamster 1999 Consensus report: Chronic periodontitis Annuals of Periodontology 4 1.
5. J. Potempa A. Banbula J. Travis 2000 Role of bacterial proteinases in matrix destruction and modulation of host responses Periodontol 2000 24 153–192.
6. L.L. Humphrey R. Fu D.I. Buckley M. Freeman M. Helfand 2008 Periodontal disease and coronary heart disease incidence: a systematic review and meta-analysis J Gen Intern Med 23 2079–2086.
7. R.C. Oliver T. Tervonen 1993 Periodontitis and tooth loss: comparing diabetics with the general population J Am Dent Assoc 124 71–76.
8. P.P. Katz M.R. Wirthlin Jr. S.M. Szpunar J.V. Selby S.J. Sepe J.A. Showstack 1991 Epidemiology and prevention of periodontal disease in individuals with diabetes Diabetes Care 14 375–385.
9. I. Smolik D. Robinson H.S. El-Gabalawy 2009 Periodontitis and rheumatoid arthritis: epidemiologic, clinical, and immunologic associations Compend Contin Educ Dent 30 188–190.
10. P. de Pablo I.L. Chapple C.D. Buckley T. Dietrich 2009 Periodontitis in systemic rheumatic diseases Nat Rev Rheumatol 5 218–224.
11. A.R. Kamer R.G. Craig A.P. Dasanayake M. Brys L. Glodzik-Sobanska M.J. de Leon 2008 Inflammation andAlzheimer's disease: possible role of periodontal diseases Alzheimers Dement 4 242–250.
12. A.R. Kamer R.G. Craig E. Pirraglia A.P. Dasanayake R.G. Norman R.J. Boylan et al.2009 TNF-alpha and antibodies to periodontal bacteria discriminate between Alzheimer's disease patients and normal subjects J Neuroimmunol 216 92–97.
13. A.R. Kamer A.P. Dasanayake R.G. Craig L. Glodzik-Sobanska M. Bry M.J. de Leon 2008 Alzheimer's disease and peripheral infections: the possible contribution from periodontal infections, model and hypothesis J Alzheimers Dis 13 437–449.
14. W.J. Loesche 1976 Chemotherapy of dental plaque infections Oral Sci Rev 9 65–107.
15. S.S. Socransky A.D. Haffajee M.A. Cugini C. Smith R.L. Kent Jr. 1998 Microbial complexes in subgingival plaque J Clin Periodontol 25 134–144.
16. S.S. Socransky A.D. Haffajee 2005 Periodontal microbial ecology Periodontol 2000 38 135–187.
17. W.E. Moore L.V. Holdeman E.P. Cato R.M. Smibert J.A. Burmeister R.R. Ranney 1983 Bacteriology of moderate (chronic) periodontitis in mature adult humans Infect Immun 42 510–515.
18. S.C. Holt L. Kesavalu S. Walker C.A. Genco 1999 Virulence factors of Porphyromonas gingivalis Periodontol 2000 20 168–238.
19. S.S. Socransky A.D. Haffajee 1994 Evidence of bacterial etiology: a historical perspective Periodontol 2000 5 7–25.
20. S.C. Holt J. Ebersole J. Felton M. Brunsvold K.S. Kornman 1988 Implantation of Bacteroides gingivalis in nonhuman primates initiates progression of periodontitis Science 239 55–57.
21. J. Slots M.A. Listgarten 1988 Bacteroides gingivalis, Bacteroides intermedius and Actinobacillus actinomycetemcomitans in human periodontal diseases J Clin Periodontol 15 85–93.
22. T.J. van Steenbergen A.J. van Winkelhoff U. van der Velden J. de Graaff 1989 Taxonomy, virulence and epidemiology of black-pigmented Bacteroides species in relation to oral infections Infection 17 194–196.
23. R.D. Pathirana N.M. O'Brien-Simpson P.D. Veith P.F. Riley E.C. Reynolds 2006 Characterization of proteinase-adhesin complexes of Porphyromonas gingivalis Microbiology 152 2381–2394.
24. R.J. Lamont H.F. Jenkinson 1998 Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis Microbiol Mol Biol Rev 62 1244–1263.
25. J. Potempa A. Sroka T. Imamura J. Travis 2003 Gingipains, the major cysteine proteinases and virulence factors of Porphyromonas gingivalis: structure, function and assembly of multidomain protein complexes Curr Protein Pept Sci 4 397–407.
26. D. Mayrand S.C. Holt 1988 Biology of asaccharolytic black-pigmented Bacteroides species Microbiol Rev 52 134–152.
27. A. Kusaba T. Ansai S. Akifusa K. Nakahigashi S. Taketani H. Inokuchi et al.2002 Cloning and expression of a Porphyromonas gingivalis gene for protoporphyrinogen oxidase by complementation of a hemG mutant of Escherichia coli Oral Microbiol Immunol 17 290–295.
28. J.M. Roper E. Raux A.A. Brindley H.L. Schubert S.E. Gharbia H.N. Shah et al.2000 The enigma of cobalamin (Vitamin B12) biosynthesis in Porphyromonas gingivalis. Identification and characterization of a functional corrin pathway J Biol Chem 275 40316–40323.
29. J.W. Smalley A.J. Birss B. Szmigielski J. Potempa 2006 The HA2 haemagglutinin domain of the lysine-specific gingipain (Kgp) of Porphyromonas gingivalis promotes micro-oxo bishaem formation from monomeric iron(III) protoporphyrin IX Microbiology 152 1839–1845.
30. M. Naito H. Hirakawa A. Yamashita N. Ohara M. Shoji H. Yukitake et al.2008 Determination of the genome sequence of Porphyromonas gingivalis strain ATCC 33277 and genomic comparison with strain W83 revealed extensive genome rearrangements in P. gingivalis DNA Res 15 215–225.
31. A. Eichinger H.G. Beisel U. Jacob R. Huber F.J. Medrano A. Banbula et al.1999 Crystal structure of gingipain R: anArg-specific bacterial cysteine proteinase with a caspase-like fold Embo J 18 5453–5462.
32. M.A. Curtis H.K. Kuramitsu M. Lantz F.L. Macrina K. Nakayama J. Potempa et al.1999 Molecular genetics and nomenclature of proteases of Porphyromonas gingivalis J Periodontal Res 34 464–472.
33. J. Potempa R. Pike J. Travis 1995 The multiple forms of trypsinlike activity present in various strains of Porphyromonas gingivalis are due to the presence of either Arg-gingipain or Lys-gingipain Infect Immun 63 1176–1182.
34. Y. Guo K.A. Nguyen J. Potempa 2010 Dichotomy of gingipains action as virulence factors: from cleaving substrates with the precision of a surgeon's knife to a meat chopper-like brutal degradation of proteins Periodontol 2000 54 15–44.
35. K. Okamoto T. Kadowaki K. Nakayama K. Yamamoto 1996 Cloning and sequencing of the gene encoding a novel lysinespecific cysteine proteinase (Lys-gingipain) in Porphyromonas gingivalis: structural relationship with the arginine-specific cysteine proteinase (Arg-gingipain) J Biochem 120 398–406.
36. N. Pavloff P.A. Pemberton J. Potempa W.C. Chen R.N. Pike V. Prochazka et al.1997 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 272 1595–1600.
37. G.A. Barkocy-Gallagher N. Han J.M. Patti J. Whitlock A. Progulske-Fox M.S. Lantz 1996 Analysis of the prtP gene encoding porphypain, a cysteine proteinase of Porphyromonas gingivalis J Bacteriol 178 2734–2741.
38. N. Slakeski P.S. Bhogal N.M. O'Brien-Simpson E.C. Reynolds 1998 Characterization of a second cell-associatedArg-specific cysteine proteinase of Porphyromonas gingivalis and identification of an adhesin-binding motif involved in association of the prtR and prtK proteinases and adhesins into large complexes Microbiology 144 1583–1592.
39. K. Okamoto K. Nakayama T. Kadowaki N. Abe D.B. Ratnayake K. Yamamoto 1998 Involvement of a lysine-specific cysteine proteinase in hemoglobin adsorption and heme accumulation by Porphyromonas gingivalis J Biol Chem 273 21225–21231.
40. N. Pavloff J. Potempa R.N. Pike V. Prochazka M.C. Kiefer J. Travis et al.1995 Molecular cloning and structural characterization of the Arg-gingipain proteinase of Porphyromonas gingivalis. Biosynthesis as a proteinase-adhesin polyprotein J Biol Chem 270 1007–1010.
41. K. Nakayama 1997 Domain-specific rearrangement between the two Arg-gingipain-encoding genes in Porphyromonas gingivalis: possible involvement of nonreciprocal recombination Microbiol Immunol 41 185–196.
42. P.S. Bhogal N. Slakeski E.C. Reynolds 1997 A cell-associated protein complex of Porphyromonas gingivalis W50 composed of Arg- and Lys-specific cysteine proteinases and adhesins Microbiology 143 2485–2495.
43. N. Slakeski S.M. Cleal P.S. Bhogal E.C. Reynolds 1999 Characterization of a Porphyromonas gingivalis gene prtK that encodes a lysine-specific cysteine proteinase and three sequence-related adhesins Oral Microbiol Immunol 14 92–97.
44. P.D. Veith G.H. Talbo N. Slakeski S.G. Dashper C. Moore R.A. Paolini et al.2002 Major outer membrane proteins and proteolytic processing of RgpA and Kgp of Porphyromonas gingivalis W50 Biochem J 363 105–115.
45. A.A. DeCarlo M. Paramaesvaran P.L. Yun C. Collyer N. Hunter 1999 Porphyrin-mediated binding to hemoglobin by the HA2 domain of cysteine proteinases (gingipains) and hemagglutinins from the periodontal pathogen Porphyromonas gingivalis J Bacteriol 181 3784–3791.
46. R. Pike W. McGraw J. Potempa J. Travis 1994 Lysine- and arginine-specific proteinases from Porphyromonas gingivalis. Isolation, characterization, and evidence for the existence of complexes with hemagglutinins J Biol Chem 269 406–411.
47. R.P. Allaker J. Aduse-Opoku J.E. Batten M.A. Curtis 1997 Natural variation within the principal arginine-specific protease gene, prpR1, of Porphyromonas gingivalis Oral Microbiol Immunol 12 298–302.
48. J. Mikolajczyk-Pawlinska T. Kordula N. Pavloff P.A. Pemberton W.C. Chen J. Travis et al.1998 Genetic variation of Porphyromonas gingivalis genes encoding gingipains, cysteine proteinases with arginine or lysine specificity Biol Chem 379 205–211.
49. N.M. O'Brien-Simpson P.D. Veith S.G. Dashper E.C. Reynolds 2003 Porphyromonas gingivalis gingipains: the molecular teeth of a microbial vampire Curr Protein Pept Sci 4 409–426.
50. M.A. Nadkarni K.A. Nguyen C.C. Chapple A.A. DeCarlo N.A. Jacques N. Hunter 2004 Distribution of Porphyromonas gingivalis biotypes defined by alleles of the kgp (Lys-gingipain) gene J Clin Microbiol 42 3873–3876.
51. K.A. Nguyen J. Travis J. Potempa 2007 Does the importance of the C-terminal residues in the maturation of RgpB from Porphyromonas gingivalis reveal a novel mechanism for protein export in a subgroup of Gram-negative bacteria? J Bacteriol 189 833–843.
52. N. Han J. Whitlock A. Progulske-Fox 1996 The hemagglutinin gene A (hagA) of Porphyromonas gingivalis 381 contains four large, contiguous, direct repeats Infect Immun 64 4000–4007.
53. R.E. Fitzpatrick L.C. Wijeyewickrema R.N. Pike 2009 The gingipains: scissors and glue of the periodontal pathogen, Porphyromonas gingivalis Future Microbiol 4 471–487.
54. K. Nakayama D.B. Ratnayake T. Tsukuba T. Kadowaki K. Yamamoto S. Fujimura 1998 Haemoglobin receptor protein is intragenically encoded by the cysteine proteinase-encoding genes and the haemagglutinin-encoding gene of Porphyromonas gingivalis Mol Microbiol 27 51–61.
55. M. Paramaesvaran K.-A. Nguyen E. Caldon J.A. McDonald S. Najdi G. Gonzaga et al.2003 Porphyrin-mediated cell surface heme capture from hemoglobin by Porphyromonas gingivalis J Bacteriol 185 2528–2537.
56. A.A. DeCarlo M. Nadkarni M. Paramaesvaran P.W. Yun C.A. Collyer N. Hunter 2004 Serum antibodies against the hemoglobin-binding domain (HA2) of Porphyromonas gingivalis J Periodontal Res 39 228–235.
57. Nguyen KA : Aspects of the innate and acquired immune response to the gingipains of Porphyromonas gingivalis. PhD thesis (2004).
58. K. Okuda J. Slots R.J. Genco 1981 Bacteroides gingivalis, Bacteroides asaccharolyticus, and Bacteroides melanogenicus sub-species: cell surface morphology and adherence to erythrocytes and human bucca epithelial cells Current Microbiology 6 7–12.
59. E. Sakai M. Naito K. Sato H. Hotokezaka T. Kadowaki A. Kamaguchi et al.2007 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 189 3977–3986.
60. K. Okuda I. Takazoe 1974 Haemagglutinating activity of Bacteroides melaninogenicus Arch Oral Biol 19 415–416.
61. H.N. Shah S.E. Gharbia 1989 Lysis of erythrocytes by the secreted cysteine proteinase of Porphyromonas gingivalis W83 FEMS Microb Letters 52 213–217.
62. A. Weinberg C.M. Belton Y. Park R.J. Lamont 1997 Role of fimbriae in Porphyromonas gingivalis invasion of gingival epithelial cells Infect Immun 65 313–316.
63. K. Okuda T. Kato 1987 Hemagglutinating activity of lipopolysaccharides from subgingival plaque bacteria Infect Immun 55 3192–3196.
64. L. Du P. Pellen-Mussi F. Chandad C. Mouton M. Bonnaure-Mallet 1997 Fimbriae and the hemagglutinating adhesin HA-Ag2 mediate adhesion of Porphyromonas gingivalis to epithelial cells Infect Immun 65 3875–3881.
65. T. Ogawa H. Uchida K. Amino 1994 Immunobiological activities of chemically defined lipid A from lipopolysaccharides of Porphyromonas gingivalis Microbiology 140 1209–1216.
66. Y. Shi D.B. Ratnayake K. Okamoto N. Abe K. Yamamoto K. Nakayama 1999 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 274 17955–17960.
67. V. Booth F.P. Ashley T. Lehner 1996 Passive immunization with monoclonal antibodies against Porphyromonas gingivalis in patients with periodontitis Infect Immun 64 422–427.
68. M.A. Curtis J. Aduse-Opoku J.M. Slaney M. Rangarajan V. Booth J. Cridland et al.1996 Characterization of an adherence and antigenic determinant of the ArgI protease of Porphyromonas gingivalis which is present on multiple gene products Infect Immun 64 2532–2539.
69. V. Booth T. Lehner 1997 Characterization of the Porphyromonas gingivalis antigen recognized by a monoclonal antibody which prevents colonization by the organism J Periodontal Res 32 54–60.
70. C.G. Kelly V. Booth H. Kendal J.M. Slaney M.A. Curtis T. Lehner 1997 The relationship between colonization and haemagglutination inhibiting and B cell epitopes of Porphyromonas gingivalis Clin Exp Immunol 110 285–291.
71. Y. Shibata M. Hayakawa H. Takiguchi T. Shiroza Y. Abiko 1999 Determination and characterization of the hemagglutinin-associated short motifs found in Porphyromonas gingivalis multiple gene products J Biol Chem 274 5012–5020.
72. R.N. Pike J. Potempa W. McGraw T.H. Coetzer J. Travis 1996 Characterization of the binding activities of proteinase-adhesin complexes from Porphyromonas gingivalis J Bacteriol 178 2876–2882.
73. C. Signas G. Raucci K. Jonsson P.E. Lindgren G.M. Anantharamaiah M. Hook et al.1989 Nucleotide sequence of the gene for a fibronectin-binding protein from Staphylococcus aureus: use of this peptide sequence in the synthesis of biologically active peptides Proc NatlAcad Sci USA 86 699–703.
74. L. Chu T.E. Bramanti J.L. Ebersole S.C. Holt 1991 Hemolytic activity in the periodontopathogen Porphyromonas gingivalis: kinetics of enzyme release and localization Infect Immun 59 1932–1940.
75. J.P. Lewis J.A. Dawson J.C. Hannis D. Muddiman F.L. Macrina 1999 Hemoglobinase activity of the lysine gingipain protease (Kgp) of Porphyromonas gingivalis W83 J Bacteriol 181 4905–4913.
76. H. Hayashi A. Nagata D. Hinode M. Sato R. Nakamura 1992 Survey of a receptor protein in human erythrocytes for hemagglutinin of Porphyromonas gingivalis Oral Microbiol Immunol 7 204–211.
77. T.E. Bramanti S.C. Holt 1991 Roles of porphyrins and host iron transport proteins in regulation of growth of Porphyromonas gingivalis W50 J Bacteriol 173 7330–7339.
78. A. Sroka M. Sztukowska J. Potempa J. Travis C.A. Genco 2001 Degradation of host heme proteins by lysine- and argininespecific cysteine proteinases (gingipains) of Porphyromonas gingivalis J Bacteriol 183 5609–5616.
79. S. Shizukuishi K. Tazaki E. Inoshita K. Kataoka T. Hanioka A. Amano 1995 Effect of concentration of compounds containing iron on the growth of Porphyromonas gingivalis FEMS Microbiol Lett 131 313–317.
80. H.N. Shah R. Bonnett B. Mateen R.A. Williams 1979 The porphyrin pigmentation of subspecies of Bacteroides melaninogenicus Biochem J 180 45–50.
81. R.J. Gibbons J.B. Macdonald 1960 Hemin and Vitamin K compounds as required factors for the cultivation of certain strains of Bacteroides melaninogenicus J Bacteriol 80 164–170.
82. T. Olczak D.W. Dixon C.A. Genco 2001 Binding specificity of the Porphyromonas gingivalis heme and hemoglobin receptor HmuR, gingipain K, and gingipain R1 for heme, porphyrins, and metalloporphyrins J Bacteriol 183 5599–5608.
83. S. Fujimura Y. Shibata K. Hirai T. Nakamura 1996 Binding of hemoglobin to the envelope of Porphyromonas gingivalis and isolation of the hemoglobin-binding protein Infect Immun 64 2339–2342.
84. J.W. Smalley A.J. Birss J. Silver 2000 The periodontal pathogen Porphyromonas gingivalis harnesses the chemistry of the mu-oxo bishaem of iron protoporphyrin IX to protect against hydrogen peroxide FEMS Microbiol Lett 183 159–164.
85. J.W. Smalley M.F. Thomas A.J. Birss R. Withnall J. Silver 2004 A combination of both arginine- and lysine-specific gingipain activity of Porphyromonas gingivalis is necessary for the generation of the micro-oxo bishaem-containing pigment from haemoglobin Biochem J 379 833–840.
86. J.W. Smalley A.J. Birss B. Szmigielski J. Potempa 2007 Sequential action of R- and K-specific gingipains of Porphyromonas gingivalis in the generation of the haem-containing pigment from oxyhaemoglobin Arch Biochem Biophys 465 44–49.
87. J.L. Gao K.A. Nguyen N. Hunter 2010 Characterization of a hemophore-like protein from Porphyromonas gingivalis J Biol Chem 285 40028–40038.
88. H. Oda K. Saiki Y. Numabe K. Konishi 2007 Effect of gamma-immunoglobulin on the asaccharolytic growth of Porphyromonas gingivalis J Periodontal Res 42 438–442.
89. D. Grenier S. Roy F. Chandad P. Plamondon M. Yoshioka K. Nakayama et al.2003 Effect of inactivation of the Arg- and/or Lys-gingipain gene on selected virulence and physiological properties of Porphyromonas gingivalis Infect Immun 71 4742–4748.
90. T. Kadowaki K. Nakayama F. Yoshimura K. Okamoto N. Abe K. Yamamoto 1998 Arg-gingipain acts as a major processing enzyme for various cell surface proteins in Porphyromonas gingivalis J Biol Chem 273 29072–29076.
91. G. Diamond N. Beckloff L.K. Ryan 2008 Host defense peptides in the oral cavity and the lung: similarities and differences J Dent Res 87 915–927.
92. A. Lala A. Amano H.T. Sojar S.J. Radel E. De Nardin 1994 Porphyromonas gingivalis trypsin-like protease: a possible natural ligand for the neutrophil formyl peptide receptor Biochem Biophys Res Commun 199 1489–1496.
93. T. Kadowaki M. Yoneda K. Okamoto K. Maeda K. Yamamoto 1994 Purification and characterization of a novel arginine-specific cysteine proteinase (argingipain) involved in the pathogenesis of periodontal disease from the culture supernatant of Porphyromonas gingivalis J Biol Chem 269 21371–21378.
94. M.A. Jagels J.A. Ember J. Travis J. Potempa R. Pike T.E. Hugli 1996 Cleavage of the human C5A receptor by proteinases derived from Porphyromonas gingivalis: cleavage of leukocyte C5a receptor Adv Exp Med Biol 389 155–164.
95. M.A. Jagels J. Travis J. Potempa R. Pike T.E. Hugli 1996 Proteolytic inactivation of the leukocyte C5a receptor by proteinases derived from Porphyromonas gingivalis Infection & Immunity 64 1984–1991.
96. M.C. Peitsch J. Tschopp 1991 Assembly of macromolecular pores by immune defense systems Curr Opin Cell Biol 3 710–716.
97. R.C. Page H.E. Schroeder 1976 Pathogenesis of inflammatory periodontal disease. A summary of current work Lab Invest 34 235–249.
98. M. Kjeldsen P. Holmstrup K. Bendtzen 1993 Marginal periodontitis and cytokines: a review of the literature J Periodontol 64 1013–1022.
99. M. Wilson R. Seymour B. Henderson 1998 Bacterial perturbation of cytokine networks Infect Immun 66 2401–2409.
100. R. Takii T. Kadowaki A. Baba T. Tsukuba K. Yamamoto 2005 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 73 883–893.
101. K. Matsushita T. Imamura S. Tancharoen S. Tatsuyama M. Tomikawa J. Travis et al.2006 Selective inhibition of Porphyromonas gingivalis growth by a factor Xa inhibitor, DX-9065a J Periodontal Res 41 171–176.
102. A.A. DeCarlo Jr. L.J. Windsor M.K. Bodden G.J. Harber B. Birkedal-Hansen H. Birkedal-Hansen 1997 Activation and novel processing of matrix metalloproteinases by a thiol-proteinase from the oral anaerobe Porphyromonas gingivalis J Dent Res 76 1260–1270.
103. R. Grayson C. Douglas J. Heath A. Rawlinson G. Evans 2003 Activation of human matrix metalloproteinase 2 by gingival crevicular fluid and Porphyromonas gingivalis J Clin Periodontol 30 542–550.
104. D. Nelson J. Potempa T. Kordula J. Travis 1999 Purification and characterization of a novel cysteine proteinase (periodontain) from Porphyromonas gingivalis. Evidence for a role in the inactivation of human alpha1-proteinase inhibitor J Biol Chem 274 12245–12251.
105. J. Potempa R. Pike J. Travis 1997 Titration and mapping of the active site of cysteine proteinases from Porphyromonas gingivalis (gingipains) using peptidyl chloromethanes Biol Chem 378 223–230.
106. T. Into M. Inomata Y. Kanno T. Matsuyama M. Machigashira Y. Izumi et al.2006 Arginine-specific gingipains from Porphyromonas gingivalis deprive protective functions of secretory leucocyte protease inhibitor in periodontal tissue Clin Exp Immunol 145 545–554.
107. T. Kantyka T. Latendorf O. Wiedow J. Bartels R. Glaser G. Dubin et al.2009 Elafin is specifically inactivated by RgpB from Porphyromonas gingivalis by distinct proteolytic cleavage Biol Chem 390 1313–1320.
108. R.D. Finn J. Tate J. Mistry P.C. Coggill S.J. Sammut H.R. Hotz et al.2008 The Pfam protein families database NucleicAcids Res 36 D281–288.
109. N. Li P. Yun M.A. Nadkarni N.B. Ghadikolaee K.A. Nguyen M. Lee et al.2010 Structure determination and analysis of a haemolytic gingipain adhesin domain from Porphyromonas gingivalis Molecular Microbiology 76 861–873.
110. M.A. Larkin G. Blackshields N.P. Brown R. Chenna P.A. McGettigan H. McWilliam F. Valentin I.M. Wallace A. Wilm R. Lopez J.D. Thompson T.J. Gibson D.G. Higgins 2007 ClustalW and Clustal X version 2.0 Bioinformatics 23 2947–2948.