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

7 tent with an immune-suppressive role for the gingipains.

8 s on binding to recombinant HmuR and soluble gingipains.

9 that repressed expression of fimbriae and of gingipains.

10 ence factors including fimbrial proteins and gingipains.

11 ase activity blocks extracellular release of gingipains.

12 ully resistant to proteolytic degradation by gingipains.

13 o proteolytically processed by P. gingivalis gingipains.

14 enes encoding cysteine peptidases other than gingipains.

15 ytic protease domain similar to caspases and gingipains.

16 sttranslational additions to some of the Arg-gingipains.

17 significance of the synergistic role of the gingipains.

18 by gingipain-active W83 extracts or purified gingipains.

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

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

21 Gingipains, a class of P. gingivalis proteases, are foun

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

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

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

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

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

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

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

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

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

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

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

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

34 intact fimB allele and limited cell surface gingipain activity in P. gingivalis 381 renders this str

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

36 adation assay demonstrated that cell surface gingipain activity is higher in 33277, and an isogenic m

37 tive fimB allele and high-level cell surface gingipain activity reduce the capacity of P. gingivalis

38 Lys-gingipain activity was essentially resistant to these in

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

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

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

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

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

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

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

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

47 Furthermore, purified gingipains also induced endothelial cell detachment and

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

49 ivated by the recent biological link between gingipain and Alzheimer's disease.

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

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

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

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

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

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

56 S) promotes periodontal disease by secreting gingipains and other virulence factors.

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

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

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

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

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

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

63 Reciprocally, Ptk1 and gingipains are required for maximal flux through OCM, an

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

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

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

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

68 The specific gingipain-associated sugar moiety recognized by monoclon

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

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

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

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

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

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

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

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

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

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

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

80 no detectable protein band representing the gingipain catalytic domain.

81 Surface retention of gingipains confers resistance to neutrophil mobilization

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

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

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

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

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

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

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

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

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

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

92 el over 72 h compared to those injected with gingipain-deficient OMVs or controls.

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

94 e isolated from wild-type strain W83 and the gingipain-deficient strain DeltaK/R-ab.

95 cells (HMEC-1) displayed an OMV-associated, gingipain-dependent decrease in cell surface levels of t

96 zebrafish larval model, we investigated the gingipain-dependent effects of systemic and local hindbr

97 Collectively, these findings highlight the gingipain-dependent mechanisms of Pg-induced neuroinflam

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

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

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

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

102 an isogenic mutant strain deficient for the gingipains exhibited an increased ability to induce TLR2

103 Immunoblotting along with cryo-EM showed gingipain expression in W83 but not DeltaK/R-ab-derived

104 In nonactive gingipain extracellular protein fractions, multiple high

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

126 responses, underscoring the pivotal role of gingipains in Pg survival, microglia activation and neur

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

128 Thus, gingipain inhibition could provide a potential approach

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

130 Oral administration of gingipain inhibitors to mice with established brain infe

131 Pg/gingipain is intra- or peri-nuclearly localized primaril

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

133 ivalis are the essential cysteine peptidases gingipain K (Kgp) and R (RgpA and RgpB), which account f

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

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

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

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

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

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

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

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

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

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

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

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

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

147 RE5 by the Porphyromonas gingivalis protease gingipain K.

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

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

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

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

152 ngivalis is a keystone pathogen, and its Lys-gingipain (Kgp) virulence factor is involved in the path

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

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

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

156 fection with Pg W83 or injection of purified gingipains led to increased microglia/macrophages number

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

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

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

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

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

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

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

164 tion with wild-type Pg W83, but not with the gingipain-null mutant (DeltaK/R-ab), resulted in increas

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

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

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

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

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

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

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

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

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

174 The gingipains, Pg crucial virulence factors, have been dete

175 Moreover, these data strongly implicate gingipains present on the OMV surface in mediating these

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

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

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

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

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

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

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

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

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

185 oacoustic imaging probe for the detection of gingipain proteases secreted by P. gingivalis.

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

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

188 ation-dependent differential partitioning of gingipain proteases.

189 oding virulence factors such as fimbriae and gingipains (proteases) and genes involved in growth and

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

191 The gingipain proteinases Kgp and RgpA/B remain phosphorylat

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

212 ly involved in the hemagglutinin activity of gingipain R1.

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

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

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

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

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

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

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

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

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

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

223 her the Porphyromonas gingivalis enzyme, Arg-gingipain (Rgp) is linked to MPO and anti-CarP levels in

224 In recent years, Arg-gingipain (Rgp) triggered myeloperoxidase (MPO) release,

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

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

227 The arginine gingipains RgpA and RgpB of Porphyromonas gingivalis are

228 ct and fragmented P. gingivalis, recombinant gingipains (RgpA and RgpB), and the bacteria Escherichia

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

230 Upon proteolytic cleavage by Arg-specific gingipain (RgpB), five-fold photoacoustic enhancement an

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

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

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

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

235 coding a type IX secretion system (T9SS) for gingipain secretion and heme accumulation.

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

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

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

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

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

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

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

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

244 A gingipain substrate degradation assay demonstrated that

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

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

247 that are defective in the production of the gingipains-the proteolytic enzymes that also harbor hema

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

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

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

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

252 Our findings suggest that Pg/gingipain translocates to pancreas, particularly beta-ce

253 They are followed by a gingipain-type catalytic domain (CD), two immunoglobulin

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

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

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

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

258 W83 but not DeltaK/R-ab-derived OMVs, where gingipains were localized to the cell wall surface.

259 domain (CTD) family proteins, including the gingipains, were upregulated in 33277 relative to 381.

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