ライフサイエンスコーパス: gingipain

1 detachment mediated by Arg-gingipain and Lys-gingipain.

2 ents rendered by digestion with purified Lys-gingipain.

3 rred substrate for Lys-gingipain but not Arg-gingipain.

4 ase that is distinct from either Arg- or Lys-gingipain.

5 predictive values were higher for gingivain/ gingipain.

6 that repressed expression of fimbriae and of gingipains.

7 ence factors including fimbrial proteins and gingipains.

8 s on binding to recombinant HmuR and soluble gingipains.

9 ully resistant to proteolytic degradation by gingipains.

10 o proteolytically processed by P. gingivalis gingipains.

11 enes encoding cysteine peptidases other than gingipains.

12 ytic protease domain similar to caspases and gingipains.

13 sttranslational additions to some of the Arg-gingipains.

14 significance of the synergistic role of the gingipains.

15 by gingipain-active W83 extracts or purified gingipains.

16 d to the post-translational additions of Arg-gingipains.

17 Recent characterization of arginine-specific gingipain-1 (gingipain R1; RGP-1) revealed that the sequ

18 These results suggest that Arg-gingipain A may play a significant role in the pathogeni

19 ralized aggressive periodontitis (GAgP), and gingipains, a group of cysteine proteinases, are critica

20 rphyromonas gingivalis by cysteine-protease (gingipains) activation of the protease-activated recepto

21 elayed by preincubation of P. gingivalis W83 gingipain-active extracellular extracts with the cystein

22 and human microvascular endothelial cells to gingipain-active extracellular protein preparations and/

23 gly, in the absence of active caspases, both gingipain-active W83 extracts and purified HRgpA and Rgp

24 did not inhibit, cell detachment induced by gingipain-active W83 extracts or purified gingipains.

25 ity and leupeptin to inhibit Rgp activity in gingipain-active W83 extracts, we investigated the relat

26 Arginine- and lysine-specific gingipain activities were reduced by approximately 90 an

27 Arginine- and lysine-specific gingipain activities were reduced by approximately 97% a

28 idase activity may be involved in regulating gingipain activity and other virulence factors and may b

29 increased sensitivity to H2O2 and decreased gingipain activity compared to the parent strain.

30 he periodontal pocket and the high levels of gingipain activity detected in gingival crevicular fluid

31 We have previously shown that gingipain activity in Porphyromonas gingivalis is modula

32 Lys-gingipain activity was essentially resistant to these in

33 In contrast to the wild type, gingipain activity was increased in P. gingivalis FLL406

34 clude regulation of hemin uptake systems and gingipain activity, processes that are intimately linked

35 givalis to epithelial cells were mediated by gingipain adhesin and Rgp catalytic domains, respectivel

36 Recently, we showed that gingipain adhesin peptide A44 hijacks the host's clathri

37 pture assay that demonstrated the binding of gingipain adhesin peptides to oral epithelial cells.

38 In contrast, inhibition of Lys-gingipain affected both the Km and Vmax, suggesting that

39 The C termini of these gingipains along with other outer membrane proteins from

40 vesicle proteinase Lys-gingipain but not Arg-gingipain also cleaved the N-terminal region of the C5aR

41 Furthermore, purified gingipains also induced endothelial cell detachment and

42 wo enzymes capable of cleaving the C5aR, Lys-gingipain and a second nontryptic serine proteinase that

43 Gingivain/gingipain and bacterial DPP levels (TA and EC) at RAL si

44 black pigmented and showed growth rates and gingipain and hemolytic activities similar to those of t

45 rotease-deficient mutants, we found that Arg-gingipain and Lys-gingipain contributed to epithelial ce

46 Secretion of the Arg-gingipain and Lys-gingipain proteases was repressed unde

47 more resistant to detachment mediated by Arg-gingipain and Lys-gingipain.

48 helial cell cultures were incubated with the gingipains and hydrolysis of E-cadherin was assessed by

49 valis recombinant VimA can interact with the gingipains and several other proteins, including a siali

50 ing Arg-gingipains) and in kgp (encoding Lys-gingipain) and a double mutant with mutations in rgpA an

51 The Lys-X (Lys-gingipain) and Arg-X (Arg-gingipain) cysteine proteases

52 ith mutations in rgpA and rgpB (encoding Arg-gingipains) and in kgp (encoding Lys-gingipain) and a do

53 Furthermore, we show that gingipain antibodies promote uptake of P. gingivalis by

54 m of an infection model and establishes that gingipains are crucially linked to systemic disease and

55 owever, the specific roles of the individual gingipains are unclear.

56 ytic adhesin domains of the major proteases, gingipains, are involved in bacterium-host interactions.

57 Here we identify gingipains as the only P. gingivalis proteases responsib

58 to dysregulate innate immunity by repressing gingipain-associated degradation of interleukin-8 (IL8).

59 The specific gingipain-associated sugar moiety recognized by monoclon

60 we solved the atomic structure of the CTD of gingipain B (RgpB) from P. gingivalis, alone and togethe

61 as gingivalis secretes proteases such as Arg-gingipain B (RgpB) that activate protease-activated rece

62 virulence factors is the cysteine peptidase gingipain B (RgpB), which is the major virulence factor

63 ve enzyme was isolated and identified as Arg-gingipain B (RgpB).

64 the bacterium Porphyromonas gingivalis, Arg-gingipain-B, and we show that it contains N- and C-termi

65 The purified vesicle proteinase Lys-gingipain but not Arg-gingipain also cleaved the N-termi

66 moglobin being a preferred substrate for Lys-gingipain but not Arg-gingipain.

67 Inactivation of arginine gingipains, but not lysine gingipains, led to decreased

68 d gingipains, we determined that each of the gingipains can cleave CAMs to varying degrees with diffe

69 ce apoptotic morphology, suggesting that the gingipains can induce both caspase-dependent and caspase

70 e of wild-type cell fractions that contained gingipain catalytic activities.

71 no detectable protein band representing the gingipain catalytic domain.

72 mutants, we found that Arg-gingipain and Lys-gingipain contributed to epithelial cell rounding and de

73 , DPP7, and DPP11 together with Arg- and Lys-gingipains cooperatively liberate most dipeptides from n

74 The Lys-X (Lys-gingipain) and Arg-X (Arg-gingipain) cysteine proteases of P. gingivalis bind and

75 pathogen, Porphyromonas gingivalis, secretes gingipains, cysteine proteases implicated as the main fa

76 The virulence factors gingipains, cysteine proteinases expressed by P. gingiva

77 with beta2GPI, P. gingivalis W83, or an arg-gingipain-defective mutant of P. gingivalis (HF18).

78 s of P. gingivalis 381 with those of its Arg-gingipain-defective mutant, G-102.

79 secreted protein profile was altered in Arg-gingipain-deficient and Lys-gingipain-deficient mutants,

80 as also slightly up-regulated by an isogenic gingipain-deficient mutant, suggesting the presence of a

81 s altered in Arg-gingipain-deficient and Lys-gingipain-deficient mutants, indicating a possible role

82 ipain proteases using systemically delivered gingipain-deficient Pg mutants, which displayed signific

83 n of the beta-catenin destruction complex by gingipain-dependent proteolytic processing.

84 s spectroscopy for both chymotrypsin and Lys-gingipain digests.

85 her, these results provide evidence that the gingipains, especially Kgp, are involved in the degradat

86 We further show that gingipains, even at low nanomolar concentrations, cleave

87 In nonactive gingipain extracellular protein fractions, multiple high

88 cleavage at Arg-X peptide bonds by arginine gingipains, followed by citrullination of carboxy-termin

89 binant P. gingivalis HmuR protein and native gingipains for hemoglobin, hemin, various porphyrins, an

90 Taken together, these results indicate that gingipains from P. gingivalis can alter cell adhesion mo

91 ellular protein preparations and/or purified gingipains from P. gingivalis.

92 We have shown previously that gingipains from Porphyromonas gingivalis W83 can induce

93 characterization of histatin 5 inhibition of gingipains from Porphyromonas gingivalis was carried out

94 lar outer membrane-associated proteases, the gingipains, from the oral pathogen Porphyromonas gingiva

95 ors which regulate the expression of the Arg-gingipain gene rgpA and the prtT protease gene were inve

96 Examinations of DPP- and gingipain gene-disrupted mutants indicated that DPP4, DP

97 ins possess an insertion adjacent to the Lys-gingipain gene.

98 Expression of the rgpA, rgpB, and kgp gingipain genes was unaffected in P. gingivalis FLL95 in

99 Expression of the rgpA, rgpB, and kgp gingipain genes was unaltered in P. gingivalis FLL93 com

100 ere were no changes in the expression of the gingipain genes, their activities were reduced by 60 to

101 o changes were seen in the expression of the gingipain genes.

102 We now show that the lysine-specific gingipain (gingipain K; KGP) is also biosynthesized as a

103 Arginine-specific gingipains (gingipains R) were also found to degrade hem

104 e either Arg-X or Lys-X peptide bonds (i.e., gingipains) have been characterized as predominant enzym

105 terial surface proteins such as fimbriae and gingipain hemagglutinin domains have been implicated as

106 GAgP patients develop specific antibodies to gingipains; however, the function of these antibodies in

107 cysteine proteinases, including Arg-specific gingipains HRGP and RGP2 and Lys-specific KGP, to degrad

108 pared the degradative abilities of the whole gingipains HRgpA and Kgp to those of their catalytic dom

109 crevicular fluid could implicate a role for gingipains in the destruction of the highly vascular per

110 ed the zebrafish model to show efficacy of a gingipain inhibitor (KYT) on Pg-mediated systemic diseas

111 n/activation of the Porphyromonas gingivalis gingipains is poorly understood.

112 n/activation of the Porphyromonas gingivalis gingipains is poorly understood.

113 Two peptidases, gingipain K (Kgp) and R (RgpA and RgpB), which differ in

114 nes encoding the lysine-specific proteinase, gingipain K (kgp) and the arginine-specific proteinase,

115 emoglobin and heme receptor HmuR, as well as gingipain K (Kgp), a lysine-specific cysteine protease,

116 in the catalytic domains of gingipain R1 and gingipain K (peptide C), followed by challenge with P. g

117 ient in lysine-specific cysteine proteinase (gingipain K [Kgp]) resulted in an increase in both IL-8

118 za-Orn derivatives were potent inhibitors of gingipain K and clostripain.

119 and transferrin but also with an increase in gingipain K and gingipain R activity.

120 ays, using either the 95-kDa gingipain R1 or gingipain K as the competing soluble antigen, indicated

121 ipains R (gingipain R1 and gingipain R2) and gingipain K produced by Porphyromonas gingivalis are vir

122 The ability of gingipain K to cleave hemoglobin, haptoglobin, and hemop

123 ecific cysteine proteinase of P. gingivalis (gingipain K, Kgp) can efficiently cleave hemoglobin, hem

124 t-killed bacteria recognize gingipain R1 and gingipain K, respectively; however, even at very high co

125 h, in addition, can activate KLKs because of gingipain K-mediated proteolytic processing of the zymog

126 now show that the lysine-specific gingipain (gingipain K; KGP) is also biosynthesized as a polyprotei

127 genes while decreasing expression of the Lys-gingipain kgp gene as detected by Northern blot analysis

128 egraded by the P. gingivalis lysine-specific gingipain (Kgp) in human endothelial cells, which correl

129 By comparing arg- (Rgp) and lys-gingipain (Kgp) mutants, a mutant deficient in both prot

130 rginine-gingipain (Rgp)A-, RgpB-, and lysine-gingipain (Kgp)-specific IgG (Kgp > RgpA > P. gingivalis

131 P. gingivalis secretes proteolytic gingipains (Kgp and RgpA/B) as zymogens inhibited by a p

132 monolayers of MDCK cells were exposed to the gingipains, Kgp was most effective in hydrolyzing the E-

133 ation of arginine gingipains, but not lysine gingipains, led to decreased citrullination.

134 In contrast to Arg-gingipain, Lys-gingipain was not inhibited by hemin, sug

135 These results suggest that Arg-gingipain may play both direct and indirect roles in the

136 Here we hypothesize that gingipains may be linked to systemic pathologies through

137 sting that the maturation pathway of the Arg-gingipains may be linked to the biosynthesis of a surfac

138 endothelial cells through both fimbriae and gingipain-mediated mechanisms.

139 yers of epithelial cells using wild-type and gingipain mutant strains.

140 Thus, we postulate that the Lys-gingipain of P. gingivalis is a hemoglobinase which play

141 Cysteine proteases, including Arg-gingipain of Porphyromonas gingivalis, have been implica

142 termine if the arginine- and lysine-specific gingipains of P. gingivalis (i.e., HRgpA and RgpB, and K

143 ted using monoclonal antibodies that the Arg-gingipains of P. gingivalis are post-translationally mod

144 The Arg- and Lys-gingipains of Porphyromonas gingivalis are important vir

145 e secretion, processing, and/or anchorage of gingipains on the cell surface.

146 l crevicular fluid (GCF) bacterial gingivain/gingipain or dipeptidyl peptidase (DPP) levels, total ac

147 translation, transport, or maturation of the gingipains, P. gingivalis FLL92 was further characterize

148 of wild-type and mutant strains, recognized gingipain peptides as adhesins rather than fimbriae.

149 The use of mutants deficient in gingipain production, along with gingipain-specific inhi

150 Kgp is the major Lys-gingipain protease of P. gingivalis and appears to be in

151 cause increased fetal loss may be on the arg-gingipain protease of P. gingivalis.

152 of these that are required for secretion of gingipain protease virulence factors by its T9SS.

153 lis PorP, which is required for secretion of gingipain protease virulence factors via the P. gingival

154 gingivalis PorSS is involved in secretion of gingipain protease virulence factors.

155 lis PorW, which is required for secretion of gingipain protease virulence factors.

156 th P. gingivalis proteases, the Arg- and Lys-gingipain proteases did not appear to be solely responsi

157 the role of the Porphyromonas gingivalis Arg-gingipain proteases in the virulence of this organism, a

158 then used to probe the role of Pg expressed gingipain proteases using systemically delivered gingipa

159 Secretion of the Arg-gingipain and Lys-gingipain proteases was repressed under these conditions

160 These results indicate that the gingipain proteinases elaborated by P. gingivalis are ca

161 The gingipain proteinases Kgp and RgpA/B remain phosphorylat

162 gingipain-specific inhibitors, revealed that gingipain proteolytic activity was required for beta-cat

163 but also with an increase in gingipain K and gingipain R activity.

164 hortened by these proteinases, with a 95-kDa gingipain R containing adhesin domains being 5-fold more

165 old more efficient in comparison to a 50-kDa gingipain R containing the catalytic domain alone.

166 multiple antigenic peptide (MAP)-conjugated gingipain R-derived peptides and then challenged with P.

167 The cysteine proteinases referred to as gingipains R (gingipain R1 and gingipain R2) and gingipa

168 terminal sequence of the catalytic domain of gingipains R (peptide A) followed by challenge with P. g

169 compassing the catalytic cysteine residue of gingipains R (peptide B) or an identical sequence within

170 o-terminal region of the catalytic domain of gingipains R are capable of inducing a protective immune

171 To examine the effect of immunization with gingipains R on the ability of P. gingivalis to colonize

172 Arginine-specific gingipains (gingipains R) were also found to degrade hemopexin and t

173 tissue lymphoma translocation protein 1) and gingipain-R.

174 p), a lysine-specific cysteine protease, and gingipain R1 (HRgpA), one of two arginine-specific cyste

175 within the adhesion/hemagglutinin domain of gingipain R1 (peptide D) which have been shown to be dir

176 cal sequence within the catalytic domains of gingipain R1 and gingipain K (peptide C), followed by ch

177 nization with heat-killed bacteria recognize gingipain R1 and gingipain K, respectively; however, eve

178 ine proteinases referred to as gingipains R (gingipain R1 and gingipain R2) and gingipain K produced

179 mmunosorbent assays, using either the 95-kDa gingipain R1 or gingipain K as the competing soluble ant

180 Immunization of mice with the 95-kDa gingipain R1, the 50-kDa gingipain R2, or a peptide deri

181 immunized intraperitoneally with the 95-kDa gingipain R1, the 50-kDa gingipain R2, or multiple antig

182 ly involved in the hemagglutinin activity of gingipain R1.

183 terization of arginine-specific gingipain-1 (gingipain R1; RGP-1) revealed that the sequence is uniqu

184 (kgp) and the arginine-specific proteinase, gingipain R2 (rgpB).

185 even at very high concentrations, the 50-kDa gingipain R2 did not hinder IgG binding to P. gingivalis

186 eferred to as gingipains R (gingipain R1 and gingipain R2) and gingipain K produced by Porphyromonas

187 ice with the 95-kDa gingipain R1, the 50-kDa gingipain R2, or a peptide derived from the N-terminal s

188 lly with the 95-kDa gingipain R1, the 50-kDa gingipain R2, or multiple antigenic peptide (MAP)-conjug

189 All three gingipains rapidly degraded TNF-alpha as exhibited by im

190 dherin immunoprecipitates with the different gingipains resulted in an effective and similar hydrolys

191 inetic analysis of the inhibition of the Arg-gingipain revealed that histatin 5 is a competitive inhi

192 experiments suggested that arginine-specific gingipain (Rgp) catalytic activity modulated adhesion.

193 elevated levels of P. gingivalis-, arginine-gingipain (Rgp)A-, RgpB-, and lysine-gingipain (Kgp)-spe

194 Suffusion of gingipain RgpA (GRgpA) elicited a significant concentrat

195 The arginine gingipains RgpA and RgpB of Porphyromonas gingivalis are

196 Furthermore, the gingipain RgpB is excreted in an inactive form in the vi

197 The Arg-gingipains (RgpsA and B) of Porphyromonas gingivalis are

198 bacterial proteinases and indicates that the gingipain Rs could be responsible for the production of

199 two arginine-specific cysteine proteinases (gingipain Rs) from Porphyromonas gingivalis, a causative

200 ongly suggesting that factor X activation by gingipain Rs, especially the 95-kDa form which is strong

201 e polysaccharide and membrane-associated Rgp gingipain showed no immunoreactivity with these fraction

202 usceptible to cleavage at both potential Lys-gingipain sites (i.e., between residues 17 and 18 [K-D]

203 In this study, we defined the levels of gingipain-specific antibodies in GAgP patient sera and e

204 ingivalis by PMNs, and our data suggest that gingipain-specific antibodies may be important for the c

205 AgP patient sera and examined the ability of gingipain-specific antibodies to facilitate opsonophagoc

206 molecular-weight proteins immunoreacted with gingipain-specific antibodies.

207 ossess elevated levels of P. gingivalis- and gingipain-specific IgG.

208 eficient in gingipain production, along with gingipain-specific inhibitors, revealed that gingipain p

209 ne-specific cysteine proteinases, designated gingipains, that consist of several tightly associated p

210 Uniquely for gingipains, the isolated Kgp pro-domain dimerized throug

211 The ability of the Lys-gingipain to cleave human hemoglobin at Lys residues was

212 healthy saliva and confirmed the ability of gingipains to inactivate SPINK6 under ex vivo conditions

213 We also mapped the cleavage by Arg-specific gingipains to the reactive site loop of the SPINK6 inhib

214 ce element IS1126 and (ii) the modulation of gingipain transcription and translation as a result of I

215 In contrast to Arg-gingipain, Lys-gingipain was not inhibited by hemin, suggesting that th

216 Using purified gingipains, we determined that each of the gingipains ca

217 The GCF levels of gingivain/gingipain were always higher than those of DPP.

218 terial peptidylarginine deiminases (PADs) or gingipains were created to assess the role of these enzy

219 ly, we demonstrate the double-edge action of gingipains, which, in addition, can activate KLKs becaus