Information on EC 3.4.22.37 - gingipain R

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The expected taxonomic range for this enzyme is: Porphyromonas gingivalis

EC NUMBER
COMMENTARY
3.4.22.37
-
RECOMMENDED NAME
GeneOntology No.
gingipain R
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
hydrolysis of proteins and small molecule substrates, with a preference for Arg in P1
show the reaction diagram
-
-
-
-
hydrolysis of proteins and small molecule substrates, with a preference for Arg in P1
show the reaction diagram
Cys244-His211 catalytic diad and a nearby Glu arranged around the S1 specificity pocket, which carries an Asp residue to enforce preference for Arg-P1 residues, mechanism and binding mode at the active site
-
hydrolysis of proteins and small molecule substrates, with a preference for Arg in P1
show the reaction diagram
proteolysis of selected proteins
P95493, -, Q51844
hydrolysis of proteins and small molecule substrates, with a preference for Arg in P1
show the reaction diagram
active site structure
-
hydrolysis of proteins and small molecule substrates, with a preference for Arg in P1
show the reaction diagram
active site structure, role of the Sn binding pocket, molecular basis for substrate specificity
-
hydrolysis of proteins and small molecule substrates, with a preference for Arg in P1
show the reaction diagram
proteolysis of selected proteins
Porphyromonas gingivalis ATCC33277
-
-
hydrolysis of proteins and small molecule substrates, with a preference for Arg in P1
show the reaction diagram
active site structure, role of the Sn binding pocket, molecular basis for substrate specificity; Cys244-His211 catalytic diad and a nearby Glu arranged around the S1 specificity pocket, which carries an Asp residue to enforce preference for Arg-P1 residues, mechanism and binding mode at the active site
Porphyromonas gingivalis HG66
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
hydrolysis of peptide bond
Porphyromonas gingivalis A7436, Porphyromonas gingivalis ATCC33277, Porphyromonas gingivalis HG66
-
-
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Arg-gingipain
-
-
-
-
Arg-gingipain
-
cysteine protease
Arg-gingipain
-
cysteine proteinase
Arg-gingipain
-
cysteine proteinases, products of the genes rgpA and rgpB
Arg-gingipain
P28784, P95493
-
Arg-gingipain
Porphyromonas gingivalis ATCC33277, Porphyromonas gingivalis HG66
-
;
-
Arg-gingipains B
-
-
Arg-gingivain-55 proteinase
-
-
-
-
Arg-gingivain-70 proteinase
-
-
-
-
Arg-gingivain-75 proteinase
-
-
-
-
Arg-gingivain-specific proteinase
-
-
Arg-gingivain-specific proteinase
Porphyromonas gingivalis ATCC33277
-
-
-
Arg-ginigipain A
-
-
Arg-ginigipain B
-
-
Arg-specific cysteine protease
-
-
Arg-specific cysteine protease
Porphyromonas gingivalis HG66
-
-
-
Arg-specific cysteine proteinase gingipain
-
-
Arg-specific gingipain protease
-
-
Arg-X proteinase
-
-
Argingipain
-
-
-
-
arginine gingipain
-
-
arginine-gingipain
-
-
Arginine-specific cysteine protease
-
-
-
-
Arginine-specific cysteine protease
-
-
Arginine-specific cysteine protease
Porphyromonas gingivalis A7436, Porphyromonas gingivalis ATCC33277
-
-
-
arginine-specific cysteine proteinase
Q51844
-
arginine-specific cysteine proteinase
Porphyromonas gingivalis HG66
Q51844
-
-
Arginine-specific gingipain
-
-
-
-
Arginine-specific gingipain
Porphyromonas gingivalis A7436
-
-
-
Arginine-specific gingipain
Porphyromonas gingivalis HG66
-
;
-
arginine-specific gingipain 2
-
-
arginine-specific gingipain proteinase
-
-
Arginine-specific gingivain
-
-
-
-
arginine-X specific cysteine proteinase
-
-
gingipain R
Porphyromonas gingivalis ATCC33277
-
-
-
gingipain R2
-
-
gingipain R2
Q51844
two different enzymes gingipain R exist in Porphyromonas gingivalis, that are encoded by related but individual genes
gingipain R2
Porphyromonas gingivalis HG66
Q51844
two different enzymes gingipain R exist in Porphyromonas gingivalis, that are encoded by related but individual genes
-
Gingipain-1
-
-
-
-
Gingivain, arginine-specific
-
-
-
-
high-molecular-mass arginine-specific gingipain
-
-
high-molecular-mass arginine-specific gingipain
Porphyromonas gingivalis HG66
-
-
-
HRgpA
-
high molecular weight form containing both catalytic and adhesin subunit
HRgpA
-
isofrom encoded by the rgpA gene
HRgpA
Porphyromonas gingivalis A7436, Porphyromonas gingivalis HG66
-
-
-
HrgpB
-
isofrom encoded by the rgpB gene
mt-RgpA
-
membrane type of enzyme, isofrom encoded by the rgpA gene
mt-RgpB
-
isofrom encoded by the rgpB gene
RgB
Porphyromonas gingivalis HG66
-
-
-
RGP
-
-
-
-
RGP
Porphyromonas gingivalis ATCC33277, Porphyromonas gingivalis HG66
-
-
-
Rgp proteinase
-
-
RGP-1
-
-
-
-
RGP-2
Porphyromonas gingivalis HG66
Q51844
-
-
RgpA
Porphyromonas gingivalis ATCC33277, Porphyromonas gingivalis RgpA
-
-
-
RgpA proteinase
-
-
RgpA proteinase
Porphyromonas gingivalis RgpA
-
-
-
RgpA(cat)
-
isofrom encoded by the rgpA gene
RgpB
-
low molecular weight form containing only the catalytic domain and a small C-terminal segment
RgpB
Porphyromonas gingivalis A7436, Porphyromonas gingivalis ATCC33277
-
-
-
RgpB
Porphyromonas gingivalis HG66
-
;
-
additional information
-
the enzyme belongs to the peptidase family C25, clan CD
CAS REGISTRY NUMBER
COMMENTARY
159745-71-8
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
arginine-specific enzyme forms HRgpA and RgpB
-
-
Manually annotated by BRENDA team
ATCC33277 and different gingipain deficient mutants
-
-
Manually annotated by BRENDA team
enzyme form RgpB
-
-
Manually annotated by BRENDA team
gene rgp, RgpA and RgpB enzymes
-
-
Manually annotated by BRENDA team
gene rgpA, encoding enzyme RgpA
-
-
Manually annotated by BRENDA team
genes rgpA and rgpB, wild-type strain W50, RgpA-deficient isogenic strain W501, and RgpB-deficient isogenic strain D7
-
-
Manually annotated by BRENDA team
isoforms HRgpA and RgpB, the first containing 4 amino acid changes compared to the latter, which are D281N, Y283S, P286S, and N331K that all map to the region surrounding the active site
-
-
Manually annotated by BRENDA team
purified 95 kDa HRgpA and 50 kDa RgpB enzyme forms
-
-
Manually annotated by BRENDA team
purified enzyme forms HRgpA and RgpB
-
-
Manually annotated by BRENDA team
strain A7436, enzyme forms HRgpA and RgpB
-
-
Manually annotated by BRENDA team
strain ATCC 33277, 2 arginine-specific gingipains RGP-A and RGP-B
-
-
Manually annotated by BRENDA team
strain ATCC 33277, gene rgp, encoding enzyme Rgp
-
-
Manually annotated by BRENDA team
strain ATCC33277
-
-
Manually annotated by BRENDA team
strain ATCC33277, gene rgpB gene, enzyme gingipain R2, 4 isoforms I-IV that are indistinguishable with regard to stability, pH-optima, kinetic characteristics and proteolytic activity
SwissProt
Manually annotated by BRENDA team
strain ATCC33277, wild-type and 4 enzyme-deficient mutants, isozymes gingipains A and B, encoded by the genes rgpA and rgpB
-
-
Manually annotated by BRENDA team
strain HG66, gene rgp-1, enzyme gingipain R1
-
-
Manually annotated by BRENDA team
strain HG66, gene rgpB/rgp-2 gene, enzyme gingipain R2, 4 isoforms I-IV that are indistinguishable with regard to stability, pH-optima, kinetic characteristics and proteolytic activity
SwissProt
Manually annotated by BRENDA team
strain HG66, gingipain R2, i.e. RgpB, isozyme II
-
-
Manually annotated by BRENDA team
strains ATCC 33277 (wild type), the Rgp/Kgp-null (rgpA rgpB kgpdeficient) triple-mutant KDP136, the Kgp-null (kgp) mutant (KDP129),and an Rgp-null (rgpA rgpBdeficient) double-mutant (KDP133)
-
-
Manually annotated by BRENDA team
strains ATCC 53978 (W50) and ATCC 33277
-
-
Manually annotated by BRENDA team
strains ATCC33277 and W50/ATCC 53978
-
-
Manually annotated by BRENDA team
strains ATCC33277, a gingipain null mutant (KDP136), and a fimbria-null mutant (KDP150)
-
-
Manually annotated by BRENDA team
strains HG66, W83, and W50
-
-
Manually annotated by BRENDA team
strains W50 (wild type) and E8 (enzyme deficient strain)
-
-
Manually annotated by BRENDA team
strains W83 and FLL203 which is a periplasemic heat-shock serine protease, both strains grow at similar rate at 37C but at 42C the FLL203 strains grows more slowly and not over an OD600 of 0.9, heat treatment of bacteria at 55C results in an upregulation of the enzyme activity in W83 and a decrease in activity in FLL203
-
-
Manually annotated by BRENDA team
strains W83 and HG66
-
-
Manually annotated by BRENDA team
strains W83, 83K3 which is deficient in the sov gene that seems be required for the export of RgpB through the outer membrane
-
-
Manually annotated by BRENDA team
wild-type strain ATCC 33277
-
-
Manually annotated by BRENDA team
wild-type strain HG66
-
-
Manually annotated by BRENDA team
wild-type strain W50, and enzyme-deficient strains D7, W501, and E8, genes rgpA and rgpB
-
-
Manually annotated by BRENDA team
Porphyromonas gingivalis A7436
strain A7436, enzyme forms HRgpA and RgpB
-
-
Manually annotated by BRENDA team
Porphyromonas gingivalis ATCC33277
strain ATCC33277
-
-
Manually annotated by BRENDA team
Porphyromonas gingivalis ATCC33277
strain ATCC33277, gene rgpB gene, enzyme gingipain R2, 4 isoforms I-IV that are indistinguishable with regard to stability, pH-optima, kinetic characteristics and proteolytic activity
SwissProt
Manually annotated by BRENDA team
Porphyromonas gingivalis ATCC33277
strain ATCC33277, wild-type and 4 enzyme-deficient mutants, isozymes gingipains A and B, encoded by the genes rgpA and rgpB
-
-
Manually annotated by BRENDA team
Porphyromonas gingivalis H66
H66
-
-
Manually annotated by BRENDA team
Porphyromonas gingivalis HG66
strain HG66
-
-
Manually annotated by BRENDA team
Porphyromonas gingivalis HG66
strain HG66, gene rgp-1, enzyme gingipain R1
-
-
Manually annotated by BRENDA team
Porphyromonas gingivalis HG66
strain HG66, gene rgpB/rgp-2 gene, enzyme gingipain R2, 4 isoforms I-IV that are indistinguishable with regard to stability, pH-optima, kinetic characteristics and proteolytic activity
SwissProt
Manually annotated by BRENDA team
Porphyromonas gingivalis HG66
strain HG66, gingipain R2, i.e. RgpB, isozyme II
-
-
Manually annotated by BRENDA team
Porphyromonas gingivalis RgpA
RgpA
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
Porphyromonas gingivalis double mutant RgpA/RgpB cells do not induce apoptosis in human gingvial epithelial cells
malfunction
-
the roles of several virulence factors in homotypic biofilm development by Porphyromonas gingivalis. A RgpA/B double mutant develops channel-like biofilms with fibrillar and tall microcolonies in PBS. When this mutant is studied in diluted trypticase soy broth, there is an increase in the number of peaks and the morphology changed to taller and loosely packed biofilms. Results suggests that Rgp controlls microcolony morphology and biovolume and acts coordinately with other virulence factors such as long (FimA) and short (Mfa) fimbriae to regulate the development of mature biofilms
malfunction
-
using Porphyromonas gingivalis null mutant KDP136 (triple mutant for RgpA/RgpB/Kgp) gingipain-sensitive ligand are identified. Two proteins encoded by protein-coding sequence PGN_0748 and PGN_0728 are obtained
malfunction
-
Porphyromonas gingivalis secretes outer membrane vesicles that contain major virulence factors, including Arg-gingipain and Lys-gingipain. Proteolytic activity of Rgp is required for membrane vesicles entry. Only few Rgp-null membrane vesicles enter the cells, and these negligibly degrade transferrin receptor, whereas paxillin and focal adhesion kinase degradation is significant
malfunction
-
Porphyromonas gingivalis RgpA/B double mutant do not induce buccal edema and gingivitis in BALB/c or C57BL/6 mice
malfunction
-
human keratinocyte Rgp-deficient and Kgp-deficient double mutant cells do not cleave protease-activated recptor-1 and -2. The single Rgp-negative mutant cleaves protease-activated recptor-2
metabolism
-
methaemoglobin formation by R-gingipain facilitates extraction of haem from haemoglobin by HmuY (haem-binding protein)
physiological function
-
live Porphyromonas gingivalis can invoke gingival epithelial cell apoptosis in a time and dose dependent manner with significant apoptosis occurring between 12 and 24 hours of challenge via a gingipain-dependent mechanism. Either arginine or lysine gingipains are necessary and sufficient factors in Porphyromonas gingivalis elicited apoptosis
physiological function
-
following entry of Porphyromonas gingivalis membrane vesicles into host cells, membrane vesicle-associated gingipains degrade cellular functional molecules such as transferrin receptor and paxillin/FAK, resulting in cellular impairment, indicating that Porphyromonas gingivalis membrane vesicles are potent vehicles for transmission of virulence factors into host cells
physiological function
-
Porphyromonas gingivalis W83 (wild type), but not gingipain-deficient mutant or wild-type bacteria pretreated with gingipain inhibitors, elicit buccal edema and gingivitis in BALB/c or C57BL/6 mice. Studies in Toll-like receptors 2-/-, bradykinin B2 receptor -/-, and neutrophil-depleted C57BL/6 mice reveal that Porphyromonas gingivalis induce edema through the sequential activation of Toll-like receptors 2/neutrophils, with the initial plasma leakage being amplified by gingipain-dependent release of vasoactive kinins from plasma-borne kininogens
physiological function
-
expression pattern of cytokines and their receptors in differentiated macrophages following exposure to active and inactive forms of the gingipains (HRgpA, RgpB and Kgp), using a cDNA array, quantitative PCR and ELISA analysis is determined. The results indicate that the adhesin subunits of the high molecular weight gingipains (HRgpA and Kgp) but not low molecular weight gingipain (RgpB) mediate strong upregulation of the expression of pro-inflammatory cytokines (interleukin-1beta and colony stimulatory factor) in macrophages; expression pattern of cytokines and their receptors in differentiated macrophages following exposure to active and inactive forms of the gingipains (HRgpA, RgpB and Kgp), using a cDNA array, quantitative PCR and ELISA analysis is determined. The results indicate that the adhesin subunits of the high molecular weight gingipains (HRgpA and Kgp) mediate strong upregulation of the expression of pro-inflammatory cytokines (interleukin-1beta and colony stimulatory factor) in macrophages
physiological function
-
gingipains induce the degradation and inactivation of endothelial thrombomodulin which may promote vascular coagulation and inflammation
physiological function
-
Rgp-cleavage of protease-activated receptor-1 up-regulates expression of cytokines
physiological function
-
cysteine-activated arginine gingipain RgpB sensitizes erythrocytes to the haemolytic effect of the K2 domain of Kgp (Lys-gingipain). RgpB degrades glycophorin A thereby potentially exposing the closely associated band 3 protein on the erythrocyte surface
physiological function
-
results suggest that gingipains may have a role in the resistance of Porphyromonas gingivalis ATCC 49417 to human beta-defensin 3
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
alpha chains of haptoglobin + H2O
?
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis A7436
-
low activity, hemoglobin protects
-
?
alpha-globin + H2O
?
show the reaction diagram
-
absolutely specific cleavage of all Arg-Xaa peptides bonds, in presence of 4 M urea, because alpha-globin is not soluble at neutral pH
-
?
alpha-thrombin + H2O
beta-thrombin B-1 and B-2 chains
show the reaction diagram
-
HRgpA and RgpB, cleavage of peptide bond R383-N394
-
?
alpha1-Antichymotrypsin + H2O
?
show the reaction diagram
P95493, -, Q51844
inactivation of the substrate
-
?
alpha1-Antichymotrypsin + H2O
?
show the reaction diagram
Porphyromonas gingivalis HG66
-, Q51844
inactivation of the substrate
-
?
apoB-100 protein + H2O
?
show the reaction diagram
-
apoB-100 degradation induces LDL-modification and contributes to the onset of atherosclerosis
-
-
?
azocasein + H2O
?
show the reaction diagram
-
-
-
?
azocasein + H2O
?
show the reaction diagram
P95493, -, Q51844
synthetic chromogenic substrate
-
?
azocasein + H2O
?
show the reaction diagram
Porphyromonas gingivalis HG66
-, Q51844
synthetic chromogenic substrate
-
?
Benzoyl-Arg 4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
-
benzoyl-Arg-4-nitroanilide + H2O
benzoyl-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
Benzoyl-Ile-Glu-(gamma-ornithyl)-Gly-Arg 4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
-
benzoyl-L-arginine-4-nitroanilide + H2O
benzoyl-L-arginine + 4-nitroaniline
show the reaction diagram
-
-
-
?
benzoyl-L-arginine-4-nitroanilide + H2O
benzoyl-L-arginine + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
benzoyl-L-arginine-4-nitroanilide + H2O
benzoyl-L-arginine + 4-nitroaniline
show the reaction diagram
P95493, -, Q51844
synthetic fluorogenic substrate
-
?
benzoyl-Phe-Val-Arg-4-nitroanilide + H2O
benzoyl-Phe-Val-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
benzoyl-Pro-Phe-Arg-4-nitroanilide + H2O
benzoyl-Pro-Phe-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
benzoyl-Val-Gly-Arg-4-nitroanilide + H2O
benzoyl-Val-Gly-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
beta-globin + H2O
?
show the reaction diagram
-
absolutely specific cleavage of all Arg-Xaa peptides bonds, in presence of 4 M urea, because beta-globin is not soluble at neutral pH
-
?
beta-thrombin B-2 chain + H2O
?
show the reaction diagram
-
HRgpA and RgpB, substrate inactivation and degradation
-
?
butoxy-carbonyl-O-benzyl-Ser-Gly-Arg-4-nitroanilide + H2O
butoxy-carbonyl-O-benzyl-Ser-Gly-Arg + 4-nitroaniline
show the reaction diagram
-
best sythetic substrate
-
?
butoxy-carbonyl-Val-Leu-Gly-Arg-4-nitroanilide + H2O
butoxy-carbonyl-Val-Leu-Gly-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
Bz-L-Arg-4-nitroanilide + H2O
Bz-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
C3 protein + H2O
?
show the reaction diagram
-
-
-
-
?
C4 protein + H2O
?
show the reaction diagram
-
-
-
-
?
C5 protein + H2O
?
show the reaction diagram
-
at higher enzyme concentrations
-
-
?
CBZ-Phe-Arg-4-methyl-coumaryl-7-amide + H2O
CBZ-Phe-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
CD27 protein + H2O
?
show the reaction diagram
-
involved in reduction of T-cell function, effective even in the presence of 2.5 or 5% serum
-
-
?
cell adhesion molecule + H2O
?
show the reaction diagram
-
involved in the detachment of endothelial cells
-
-
?
Collagen type I + H2O
?
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC33277
-
not the purified isoforms, enzyme probably needs to be attached to the cell surface
-
?
D-Ile-Pro-Arg 4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
-
D-Phe-Pip-Arg 4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
-
denatured alpha1-proteinase inhibitor + H2O
?
show the reaction diagram
P95493, -, Q51844
-
-
?
denatured type I collagen + H2O
?
show the reaction diagram
P95493, -, Q51844
-
-
?
denatured type I collagen + H2O
?
show the reaction diagram
Porphyromonas gingivalis HG66
-, Q51844
-
-
?
elafin + H2O
?
show the reaction diagram
P28784, P95493
all three gingipains have the ability to degrade elafin (endogenous inhibitor secreted by epithelial cells)
-
-
?
elafin + H2O
?
show the reaction diagram
P28784, P95493
all three gingipains have the ability to degrade elafin (endogenous inhibitor secreted by epithelial cells) with RgpB being far more efficient than other gingipains. RgpB efficiently inactivates the inhibitory activity of elafin at subnanomolar concentrations through proteolysis limited to the Arg22-Cys23 peptide bond within the surface loop harboring the inhibitor active site
-
-
?
factor IX proenzyme + H2O
?
show the reaction diagram
-
activation through limited proteolysis
-
-
?
factor X proenzyme + H2O
?
show the reaction diagram
-
activation through limited proteolysis
-
-
?
fibrinogen A alpha-chain + H2O
28 kDa fragment + ?
show the reaction diagram
-
major cleavage site at position 22, all isoforms
the 28 kDa fragment is the major product of isoform HRgpA
?
fibrinogen B beta-chain + H2O
?
show the reaction diagram
-
high activity of isoform HRgpA, which performs cleavage at 2 positions: 42 and 44
-
?
Gelatin + H2O
?
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC33277
-
purified isozymes
-
?
Glycophorin A + H2O
?
show the reaction diagram
-
-
-
-
?
haemoglobin + H2O
?
show the reaction diagram
-
complete digestion, enzyme form RGP-B shows high activity, not RGP-A, human substrate
-
?
haptoglobin + H2O
?
show the reaction diagram
-
degradation of host protein substrate
-
-
?
Hemoglobin + H2O
?
show the reaction diagram
-
degradation of host protein substrate
-
-
?
hemopexin + H2O
hemin + ?
show the reaction diagram
-
-
products of 23 kDa and 47 kDa, products of 23 kDa and 40 kDa in serum
?
hemopexin + H2O
hemin + ?
show the reaction diagram
Porphyromonas gingivalis A7436
-
-
products of 23 kDa and 47 kDa, products of 23 kDa and 40 kDa in serum
?
hemopexin + H2O
?
show the reaction diagram
-
degradation of host protein substrate
-
-
?
human beta-defensin 3 + H2O
?
show the reaction diagram
-
-
-
-
?
human protease-activated receptor PAR-1 + H2O
?
show the reaction diagram
-
-, PAR-1 activation on epithelial cells
-
-
?
human protease-activated receptor PAR-1 + H2O
?
show the reaction diagram
Porphyromonas gingivalis HG66
-
-, PAR-1 activation on epithelial cells
-
-
?
human protease-activated receptor PAR-2 + H2O
?
show the reaction diagram
-
-, PAR-2 activation on epithelial cells
-
-
?
human protease-activated receptor PAR-2 + H2O
?
show the reaction diagram
Porphyromonas gingivalis HG66
-
-
-
-
?
Insulin B-chain + H2O
?
show the reaction diagram
-
specific cleavage of Arg-+-
-
-
-
integrin subunit alpha2 + H2O
?
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC33277
-
-
-
?
integrin subunit beta1 + H2O
?
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC33277
-
-
-
?
integrin subunit beta3 + H2O
?
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC33277
-
-
-
?
interferon gamma + H2O
?
show the reaction diagram
-
degradation, degradation leading to local cytokine paralysis impairing the inflammation-dependent host defense mechanisms
-
-
?
interleukin 12 + H2O
?
show the reaction diagram
-
degradation, degradation leading to local cytokine paralysis impairing the inflammation-dependent host defense mechanisms
-
-
?
interleukin-1beta + H2O
?
show the reaction diagram
-
low activity, biological inactivation and degradation, low activity, cytokine degradation is mainly the result of Lys-gingipain, EC 3.4.22.47
-
-
?
interleukin-6 + H2O
?
show the reaction diagram
-
-, biological inactivation and degradation
-
-
?
interleukin-8 + H2O
?
show the reaction diagram
-
-, biological inactivation and degradation
-
-
?
Leu-Tyr-Arg-4-nitroanilide + H2O
Leu-Tyr-Arg + 4-nitroaniline
show the reaction diagram
P95493, -, Q51844
synthetic fluorogenic substrate
-
?
Lysozyme + H2O
?
show the reaction diagram
-
absolutely specific cleavage of all Arg-Xaa peptides bonds
-
?
Mellitin + H2O
?
show the reaction diagram
-
specific cleavage of Arg-+-
-
-
-
N-alpha-benzoyl-D,L-arginine-4-nitroanilide + H2O
N-alpha-benzoyl-L-arginine + 4-nitroanilide
show the reaction diagram
-
-
-
-
?
N-alpha-benzoyl-DL-Arg-4-nitroanilide + H2O
N-alpha-benzoyl-DL-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
N-alpha-benzoyl-DL-arginine 4-nitroanilide + H2O
N-alpha-benzoyl-DL-arginine + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
N-alpha-benzoyl-DL-arginine-4-nitroanilide + H2O
N-alpha-benzoyl-DL-arginine + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
N-alpha-benzoyl-DL-Lys-4-nitroanilide + H2O
N-alpha-benzoyl-DL-Lys + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
N-alpha-benzoyl-L-arginine-4-nitroanilide + H2O
N-alpha-benzoyl-L-arginine + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
N-benzoyl-L-arginine-4-nitroanilide + H2O
N-benzoyl-L-arginine + 4-nitroaniline
show the reaction diagram
-
-
-
?
N-cadherin + H2O
?
show the reaction diagram
-
in BCAEC cells, cleavage by HRgpA but not RgpB
-
-
?
N-p-tosyl-Gly-Pro-Arg-4-nitroanilide + H2O
N-p-tosyl-Gly-Pro-Arg + 4-nitroaniline
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis HG66
-
-
-
-
?
Nalpha-benzoyl-D,L-Arg-4-nitroanilide + H2O
Nalpha-benzoyl-D,L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
Nalpha-benzoyl-L-Arg-4-nitroanilide + H2O
Nalpha-benzoyl-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
Nalpha-benzoyl-L-Arg-4-nitroanilide + H2O
Nalpha-benzoyl-L-Arg + 4-nitroanilide
show the reaction diagram
-
-
-
-
?
Nalpha-benzoyl-L-Arg-4-nitroanilide + H2O
Nalpha-benzoyl-L-Arg-4-nitroaniline
show the reaction diagram
-
-
-
-
?
oxyhaemoglobin + H2O
methaemoglobin
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis HG66
-
data indicate direct product formation without the occurrence of intermediates, reaction required for the formation the the my-oxo heam dimer containing black pigment
-
-
?
oxyhaemoglobin + H2O
methaemoglobin + ?
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis HG66
-
data indicate direct product formation without the occurrence of intermediates
-
-
?
oxyhaemoglobin + H2O
?
show the reaction diagram
-
-
-
-
?
prefimbrillin + H2O
fimbrilline + ?
show the reaction diagram
-
-
mature form of the protein
-
?
profibronectin + H2O
fibronectin + ?
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC33277
-
-
-
?
protease-activated receptor-1 + H2O
?
show the reaction diagram
-
specific substrate for Arg-gingipain
-
-
?
protein + H2O
peptides
show the reaction diagram
-
-
-
?
protein + H2O
peptides
show the reaction diagram
-
-
-
?
protein + H2O
peptides
show the reaction diagram
-
-
-
?
protein + H2O
peptides
show the reaction diagram
-
-
-
?
protein + H2O
peptides
show the reaction diagram
-
-
-
?
protein + H2O
peptides
show the reaction diagram
-
-
-
?
protein + H2O
peptides
show the reaction diagram
P95493, -, Q51844
-
-
?
protein + H2O
peptides
show the reaction diagram
Porphyromonas gingivalis HG66
-
-
-
?
protein + H2O
peptides
show the reaction diagram
Porphyromonas gingivalis HG66
-, Q51844
-
-
?
protein C + H2O
?
show the reaction diagram
-
activation through limited proteolysis
-
-
?
prothrombin + H2O
thrombin + ?
show the reaction diagram
-
HRgpA, involved in fibrinogen clotting
-
?
prothrombin + H2O
alpha-thrombin + 2 peptide fragments
show the reaction diagram
-
major cleavage sites of HRgpA are R271-T272, R320-I321, and R155-S156, activation of human substrate, HRgpA possesses adhesion domains and is about 20fold more active than the single chain RgpB
high amount od alpha-thrombin
?
prothrombin + H2O
alpha-thrombin + prethrombin 1 + prethrombin 2 + 1 peptide fragments
show the reaction diagram
-
major cleavage sites of RgpB are R155-S156 and R271-T272, while the peptide bond R320-I321 is not efficiently cleaved resulting in about 20fold slower reaction, activation of human substrate, less active than HRgpA
low amount of alpha-thrombin
?
prothrombin + H2O
?
show the reaction diagram
-
activation through limited proteolysis
-
-
?
RgpA-HagA polyprotein + H2O
?
show the reaction diagram
-
processing of the precursor by Rgp
-
-
?
RgpA-Hgp polyprotein + H2O
?
show the reaction diagram
-
processing of the precursor by Rgp, processing of the precursor by Rgp, Porphyromonas gingivalis-induced platelet aggregation in platelet-rich plasma depends on processed Hgp44 adhesin but not directly on Rgp proteinase, the adhesin is also processed by Lys-gingipain Kgp, EC 3.4.22.47
-
-
?
ribonuclease A + H2O
?
show the reaction diagram
-
absolutely specific cleavage of all Arg-Xaa peptides bonds
-
?
secretory leucocyte protease inhibitor + H2O
?
show the reaction diagram
-
reduction of the protective effect of SLPIon neutrophil proteases and bacterial proinflammatory compounds, recombinant protein, reaction catalyzed by RgpA and RgpB
-
-
?
t-butyloxycarbonyl-L-leucylglycyl-L-arginine-4-metylcoumaryl-7-amide + H2O
?
show the reaction diagram
-
-
-
-
?
thrombomodulin + H2O
?
show the reaction diagram
-
Lys-gingipain and Arg-gingipain cleave thrombomodulin in vitro
-
-
?
TNFalpha + H2O
?
show the reaction diagram
-
degradation, degradation leading to local cytokine paralysis impairing the inflammation-dependent host defense mechanisms
-
-
?
TNFalpha + H2O
?
show the reaction diagram
-
inactivation by degradation of human TNFalpha on host cell surface and recombinant fibroblast cell surface, leading to inhibition of biological functions of TNFalpha, overview, degradation, high activity with HRgpA, moderate activity with RgpB
-
-
?
toluenesulfonyl-glycyl-L-prolyl-L-arginine-4-nitroanilide + H2O
toluenesulfonyl-glycyl-L-prolyl-L-arginine + 4-nitroaniline
show the reaction diagram
-
-
-
?
tosyl-Gly-L-Pro-L-Arg 4-nitroanilide + H2O
tosyl-Gly-L-Pro-L-Arg 4-nitroaniline
show the reaction diagram
-
-
-
-
?
tosyl-GPR-4-nitroanilide + H2O
tosyl-GPR + 4-nitroaniline
show the reaction diagram
P95493, -, Q51844
other substrates with a Ps proline are very poor substrates, synthetic fluorogenic substrate
-
?
transferrin + H2O
?
show the reaction diagram
-
degradation of host protein substrate
-
-
?
transferrin + H2O
hemin + ?
show the reaction diagram
-
-, slight truncation of the polypeptide chain in serum
-
?
transferrin + H2O
hemin + ?
show the reaction diagram
Porphyromonas gingivalis A7436
-
-, slight truncation of the polypeptide chain in serum
-
?
transferring receptor + H2O
?
show the reaction diagram
-
Rgp is responsible for transferring receptor degradation
-
-
?
VE-cadherin + H2O
?
show the reaction diagram
-
in BCAEC cells, especially HRgpA
-
-
?
Z-Arg-Arg-4-nitroanilide + H2O
Z-Arg-Arg + 4-nitroaniline
show the reaction diagram
P95493, -, Q51844
synthetic fluorogenic substrate
-
?
MeoSuc-Ala-Ala-Pro-Val-4-nitroanilide + H2O
?
show the reaction diagram
P28784, P95493
-
-
-
?
additional information
?
-
-
hydrolysis of synthetic chromogenic substrates with arginine in the P1 position
-
-
-
additional information
?
-
-
no activity of both enzyme forms with toluenesulfonyl-glycyl-L-prolyl-L-lysine-4-nitroanilide, Val-Leu-Lys-4-nitroanilide, benzoyl-Lys-4-nitroanilide, succinyl-Ala-Ala-Pro-Phe-4-nitroanilide, glutaryl-Phe-4-nitroanilide, benzoyl-Tyr-4-nitroanilide, and Lys-4-nitroanilide, activity with chromogenic synthetic substrates is limited to those with arginine in the P1-position
-
?
additional information
?
-
-
substrate specificity for the C-terminal position next to the cleavage site of the different enzyme forms, overview
-
?
additional information
?
-
P95493, -, Q51844
substrate specificity, no inactivation of native alpha1-proteinase inhibitor and native type I collagen
-
?
additional information
?
-
-
the enzyme makes a significant contribution to the virulence of Porphyromonas gingivalis
-
-
-
additional information
?
-
-
enzyme disrupts interaction between fibronectin and integrin in human fibroblasts, leading to cell death of detached fibroblasts, which contributes to the tissue damage in periodontal disease caused by Porphyromonas gingivalis
-
?
additional information
?
-
-
a combination of both arginine- and lysine-specific gingipain activity is necessary for the generation of the micro-oxo bishaem-containing pigment from haemoglobin, interaction with oxyhemoglobin, overview
-
-
-
additional information
?
-
-
gingipains are essential for bacterial virulence and survival
-
-
-
additional information
?
-
-
gingipains cleave a broad range of in-host proteins and are key virulence factors in the onset and development of human adult periodontitis, the enzyme stimulates production of hepatocyte growth factor, i.e. scatter factor, through protease-activated receptors in human gingival fibroblasts in culture, overview
-
-
-
additional information
?
-
-
gingipains R are potent permeability enhancement factors by prekallikrein activation and bradykinin induction, the enzyme degrades proteins of connective tissue, cell surface proteins and receptors, cytokines and plasma proteins, including components of the coagulation and complement cascades, heme- and iron-binding proteins, immunoglobulins and proteinase inhibitors
-
-
-
additional information
?
-
-
gingipains R mediate coaggregation of Porphyromonas gingivalis with other bacteria, overview
-
-
-
additional information
?
-
-
the enzyme degrades host iron- and heme-containing proteins, regulation of enzyme expression, overview, inhibition of gingipain increases the hmuR gene expression encoding the heme/hemoglobin receptor HmuR, and decreases the cell growth in the early and middle stages, but not in the late stages
-
-
-
additional information
?
-
-
the enzyme inactivates a cell surface ligand on Porphyromonas gingivalis that induces TLR2-and TLR4-independent signaling involving CD25, but has no effect on TLR2-and TLR4-dependent signaling, overview, gingipains are cysteine proteinases
-
-
-
additional information
?
-
-
gingipains are cysteine proteinases cleaving a broad range of in-host proteins
-
-
-
additional information
?
-
-
role of the Sn binding pocket, molecular basis for substrate specificity, overview
-
-
-
additional information
?
-
-
the enzyme is specific for peptide substrate with Arg at P1 position, gingipain R performs autoprocessing and activation
-
-
-
additional information
?
-
-
implicated in a wide range of both pathological and physiological processes of Porphyromonas gingivalis, including destruction of periodontal tissue, disruption of host defense mechanisms, processing of bacterial cell surface and secretory proteins, and acquisition of heme and amino acids, involved in atherosclerotic processes
-
-
-
additional information
?
-
-
important for the provision of nutrients for the bacterium in the host organism, destruction of host tissue, modulation of host immune response
-
-
-
additional information
?
-
-
important virulence factors in periodontitis
-
-
-
additional information
?
-
-
important virulence factors in periodontitis, activation of the C1 complex in serum, degradation of multiple complement components, important factor for the resistance to the bacteriolytic activity of serum
-
-
-
additional information
?
-
-
important virulence factors in periodontitis, involved in the perturbation of host defense and the destruction and invasion of host tissues, degradation of hosts proteins such as ICAM-1m VCAM-1, catenins, and cadherins, involved in the shedding of syndecan-1
-
-
-
additional information
?
-
-
important virulence factors in periodontitis, probably involved in the reduction of T-cell function at periodontal lesion sites, induction of PAR-1 and PAR-2 receptor expression, up-regulation of PAR-4 expression, little effect on PAR-3 expression, increases expression of CD69 and CD25 on T-cells
-
-
-
additional information
?
-
-
involved in the deregulation of the hosts inflammatory response
-
-
-
additional information
?
-
-
involved in the induction of apoptosis in caspase dependent and caspase independent pathway
-
-
-
additional information
?
-
-
involved in the regulation of mRNA expression for the receptor activator of NF-kappaB ligand (RANKL) protein
-
-
-
additional information
?
-
-
no degradation of ICAM-3
-
-
-
additional information
?
-
-
extracellular gingipain protease activities cause a lack of secondary cytokine response in human cells after challenge with live Porphyromonas gingivalis
-
-
-
additional information
?
-
-
gingipains are cysteine proteinases and virulence factors of Porphyromonas gingivalis, the major causative bacterium of periodontal disease. Gingipains stimulate interleukin-8 secretion from human THP-1 cells, which is completely inhibited by proteinase inhibitors of gingipain and is increased in the presence of pathogen-associated molecular patterns, PAMPs, overview
-
-
-
additional information
?
-
-
gingipains are involved in bacterial adherence to host cells, RgpA binds to adhesin via its adhesin binding domain. Peptide A44 derived from the adhesin domain of RgpA plays a role in binding of Porphyromonas gingivalis to HEP-2 epithelial cells via cell surface receptors, e.g. clathrin, nocodazole and paclitaxel, which disrupt microtubule formation, block the interaction, while genistein does not
-
-
-
additional information
?
-
-
gingipains are key virulence determinants of Porphyromonas gingivalis and play a crucial role in pathogenicity
-
-
-
additional information
?
-
-
gingipains reduce cyclin expression and cause early G1 arrest, leading to the inhibition of cellular proliferation in murine ST2 osteoblastic/stromal cells, overview
-
-
-
additional information
?
-
-
HRgpA-mediated downregulation and RgpB-mediated upregulation of production of interleukin-8, occurs through protease-activated receptors, PAR-1 and PAR-2, signalling, RgpB-mediated upregulation of IL-8 production occurs through nuclear factor-kappa B, which does not affect HRgpA-mediated downregulation, overview. Gingipains preferentially suppress IL-8, resulting in attenuation of the cellular recognition of bacteria, and as a consequence, sustain chronic inflammation
-
-
-
additional information
?
-
-
RgpA and RgpB cleave proteins after arginine residues
-
-
-
additional information
?
-
Porphyromonas gingivalis HG66
-
gingipains cleave a broad range of in-host proteins and are key virulence factors in the onset and development of human adult periodontitis, the enzyme stimulates production of hepatocyte growth factor, i.e. scatter factor, through protease-activated receptors in human gingival fibroblasts in culture, overview, gingipains are cysteine proteinases cleaving a broad range of in-host proteins
-
-
-
additional information
?
-
Porphyromonas gingivalis HG66
-
gingipains are essential for bacterial virulence and survival, role of the Sn binding pocket, molecular basis for substrate specificity, overview
-
-
-
additional information
?
-
Porphyromonas gingivalis HG66
-
HRgpA-mediated downregulation and RgpB-mediated upregulation of production of interleukin-8, occurs through protease-activated receptors, PAR-1 and PAR-2, signalling, RgpB-mediated upregulation of IL-8 production occurs through nuclear factor-kappa B, which does not affect HRgpA-mediated downregulation, overview. Gingipains preferentially suppress IL-8, resulting in attenuation of the cellular recognition of bacteria, and as a consequence, sustain chronic inflammation
-
-
-
additional information
?
-
Porphyromonas gingivalis HG66
-, Q51844
substrate specificity, no inactivation of native alpha1-proteinase inhibitor and native type I collagen
-
?
additional information
?
-
Porphyromonas gingivalis ATCC33277
-
enzyme disrupts interaction between fibronectin and integrin in human fibroblasts, leading to cell death of detached fibroblasts, which contributes to the tissue damage in periodontal disease caused by Porphyromonas gingivalis
-
?
additional information
?
-
Porphyromonas gingivalis ATCC33277
-
gingipains reduce cyclin expression and cause early G1 arrest, leading to the inhibition of cellular proliferation in murine ST2 osteoblastic/stromal cells, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
apoB-100 protein + H2O
?
show the reaction diagram
-
apoB-100 degradation induces LDL-modification and contributes to the onset of atherosclerosis
-
-
?
C3 protein + H2O
?
show the reaction diagram
-
-
-
-
?
C4 protein + H2O
?
show the reaction diagram
-
-
-
-
?
C5 protein + H2O
?
show the reaction diagram
-
at higher enzyme concentrations
-
-
?
CD27 protein + H2O
?
show the reaction diagram
-
involved in reduction of T-cell function, effective even in the presence of 2.5 or 5% serum
-
-
?
cell adhesion molecule + H2O
?
show the reaction diagram
-
involved in the detachment of endothelial cells
-
-
?
Collagen type I + H2O
?
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC33277
-
not the purified isoforms, enzyme probably needs to be attached to the cell surface
-
?
elafin + H2O
?
show the reaction diagram
P28784, P95493
all three gingipains have the ability to degrade elafin (endogenous inhibitor secreted by epithelial cells)
-
-
?
elafin + H2O
?
show the reaction diagram
P28784, P95493
all three gingipains have the ability to degrade elafin (endogenous inhibitor secreted by epithelial cells) with RgpB being far more efficient than other gingipains. RgpB efficiently inactivates the inhibitory activity of elafin at subnanomolar concentrations through proteolysis limited to the Arg22-Cys23 peptide bond within the surface loop harboring the inhibitor active site
-
-
?
factor IX proenzyme + H2O
?
show the reaction diagram
-
activation through limited proteolysis
-
-
?
factor X proenzyme + H2O
?
show the reaction diagram
-
activation through limited proteolysis
-
-
?
Glycophorin A + H2O
?
show the reaction diagram
-
-
-
-
?
haptoglobin + H2O
?
show the reaction diagram
-
degradation of host protein substrate
-
-
?
Hemoglobin + H2O
?
show the reaction diagram
-
degradation of host protein substrate
-
-
?
hemopexin + H2O
hemin + ?
show the reaction diagram
-
-
products of 23 kDa and 40 kDa in serum
?
hemopexin + H2O
?
show the reaction diagram
-
degradation of host protein substrate
-
-
?
hemopexin + H2O
hemin + ?
show the reaction diagram
Porphyromonas gingivalis A7436
-
-
products of 23 kDa and 40 kDa in serum
?
human protease-activated receptor PAR-1 + H2O
?
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis HG66
-
PAR-1 activation on epithelial cells
-
-
?
human protease-activated receptor PAR-2 + H2O
?
show the reaction diagram
-
PAR-2 activation on epithelial cells
-
-
?
integrin subunit alpha2 + H2O
?
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC33277
-
-
-
?
integrin subunit beta1 + H2O
?
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC33277
-
-
-
?
integrin subunit beta3 + H2O
?
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC33277
-
-
-
?
interferon gamma + H2O
?
show the reaction diagram
-
degradation leading to local cytokine paralysis impairing the inflammation-dependent host defense mechanisms
-
-
?
interleukin 12 + H2O
?
show the reaction diagram
-
degradation leading to local cytokine paralysis impairing the inflammation-dependent host defense mechanisms
-
-
?
interleukin-1beta + H2O
?
show the reaction diagram
-
biological inactivation and degradation, low activity, cytokine degradation is mainly the result of Lys-gingipain, EC 3.4.22.47
-
-
?
interleukin-6 + H2O
?
show the reaction diagram
-
biological inactivation and degradation
-
-
?
oxyhaemoglobin + H2O
methaemoglobin
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis HG66
-
data indicate direct product formation without the occurrence of intermediates, reaction required for the formation the the my-oxo heam dimer containing black pigment
-
-
?
prefimbrillin + H2O
fimbrilline + ?
show the reaction diagram
-
-
mature form of the protein
-
?
profibronectin + H2O
fibronectin + ?
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC33277
-
-
-
?
protease-activated receptor-1 + H2O
?
show the reaction diagram
-
specific substrate for Arg-gingipain
-
-
?
protein + H2O
peptides
show the reaction diagram
-
-
-
?
protein + H2O
peptides
show the reaction diagram
-
-
-
?
protein + H2O
peptides
show the reaction diagram
-
-
-
?
protein + H2O
peptides
show the reaction diagram
-
-
-
?
protein + H2O
peptides
show the reaction diagram
-
-
-
?
protein + H2O
peptides
show the reaction diagram
-
-
-
?
protein + H2O
peptides
show the reaction diagram
P95493, -, Q51844
-
-
?
protein + H2O
peptides
show the reaction diagram
Porphyromonas gingivalis HG66
-
-
-
?
protein + H2O
peptides
show the reaction diagram
Porphyromonas gingivalis HG66
-, Q51844
-
-
?
protein C + H2O
?
show the reaction diagram
-
activation through limited proteolysis
-
-
?
prothrombin + H2O
thrombin + ?
show the reaction diagram
-
HRgpA, involved in fibrinogen clotting
-
?
prothrombin + H2O
?
show the reaction diagram
-
activation through limited proteolysis
-
-
?
RgpA-HagA polyprotein + H2O
?
show the reaction diagram
-
processing of the precursor by Rgp
-
-
?
RgpA-Hgp polyprotein + H2O
?
show the reaction diagram
-
processing of the precursor by Rgp, Porphyromonas gingivalis-induced platelet aggregation in platelet-rich plasma depends on processed Hgp44 adhesin but not directly on Rgp proteinase, the adhesin is also processed by Lys-gingipain Kgp, EC 3.4.22.47
-
-
?
secretory leucocyte protease inhibitor + H2O
?
show the reaction diagram
-
reduction of the protective effect of SLPIon neutrophil proteases and bacterial proinflammatory compounds
-
-
?
TNFalpha + H2O
?
show the reaction diagram
-
degradation leading to local cytokine paralysis impairing the inflammation-dependent host defense mechanisms
-
-
?
TNFalpha + H2O
?
show the reaction diagram
-
inactivation by degradation of human TNFalpha on host cell surface and recombinant fibroblast cell surface, leading to inhibition of biological functions of TNFalpha, overview
-
-
?
transferrin + H2O
?
show the reaction diagram
-
degradation of host protein substrate
-
-
?
transferrin + H2O
hemin + ?
show the reaction diagram
Porphyromonas gingivalis, Porphyromonas gingivalis A7436
-
slight truncation of the polypeptide chain in serum
-
?
transferring receptor + H2O
?
show the reaction diagram
-
Rgp is responsible for transferring receptor degradation
-
-
?
interleukin-8 + H2O
?
show the reaction diagram
-
biological inactivation and degradation
-
-
?
additional information
?
-
-
the enzyme makes a significant contribution to the virulence of Porphyromonas gingivalis
-
-
-
additional information
?
-
-
enzyme disrupts interaction between fibronectin and integrin in human fibroblasts, leading to cell death of detached fibroblasts, which contributes to the tissue damage in periodontal disease caused by Porphyromonas gingivalis
-
?
additional information
?
-
-
a combination of both arginine- and lysine-specific gingipain activity is necessary for the generation of the micro-oxo bishaem-containing pigment from haemoglobin, interaction with oxyhemoglobin, overview
-
-
-
additional information
?
-
-
gingipains are essential for bacterial virulence and survival
-
-
-
additional information
?
-
-
gingipains cleave a broad range of in-host proteins and are key virulence factors in the onset and development of human adult periodontitis, the enzyme stimulates production of hepatocyte growth factor, i.e. scatter factor, through protease-activated receptors in human gingival fibroblasts in culture, overview
-
-
-
additional information
?
-
-
gingipains R are potent permeability enhancement factors by prekallikrein activation and bradykinin induction, the enzyme degrades proteins of connective tissue, cell surface proteins and receptors, cytokines and plasma proteins, including components of the coagulation and complement cascades, heme- and iron-binding proteins, immunoglobulins and proteinase inhibitors
-
-
-
additional information
?
-
-
gingipains R mediate coaggregation of Porphyromonas gingivalis with other bacteria, overview
-
-
-
additional information
?
-
-
the enzyme degrades host iron- and heme-containing proteins, regulation of enzyme expression, overview, inhibition of gingipain increases the hmuR gene expression encoding the heme/hemoglobin receptor HmuR, and decreases the cell growth in the early and middle stages, but not in the late stages
-
-
-
additional information
?
-
-
the enzyme inactivates a cell surface ligand on Porphyromonas gingivalis that induces TLR2-and TLR4-independent signaling involving CD25, but has no effect on TLR2-and TLR4-dependent signaling, overview
-
-
-
additional information
?
-
-
implicated in a wide range of both pathological and physiological processes of Porphyromonas gingivalis, including destruction of periodontal tissue, disruption of host defense mechanisms, processing of bacterial cell surface and secretory proteins, and acquisition of heme and amino acids, involved in atherosclerotic processes
-
-
-
additional information
?
-
-
important for the provision of nutrients for the bacterium in the host organism, destruction of host tissue, modulation of host immune response
-
-
-
additional information
?
-
-
important virulence factors in periodontitis
-
-
-
additional information
?
-
-
important virulence factors in periodontitis, activation of the C1 complex in serum, degradation of multiple complement components, important factor for the resistance to the bacteriolytic activity of serum
-
-
-
additional information
?
-
-
important virulence factors in periodontitis, involved in the perturbation of host defense and the destruction and invasion of host tissues, degradation of hosts proteins such as ICAM-1m VCAM-1, catenins, and cadherins, involved in the shedding of syndecan-1
-
-
-
additional information
?
-
-
important virulence factors in periodontitis, probably involved in the reduction of T-cell function at periodontal lesion sites, induction of PAR-1 and PAR-2 receptor expression, up-regulation of PAR-4 expression, little effect on PAR-3 expression, increases expression of CD69 and CD25 on T-cells
-
-
-
additional information
?
-
-
involved in the deregulation of the hosts inflammatory response
-
-
-
additional information
?
-
-
involved in the induction of apoptosis in caspase dependent and caspase independent pathway
-
-
-
additional information
?
-
-
involved in the regulation of mRNA expression for the receptor activator of NF-kappaB ligand (RANKL) protein
-
-
-
additional information
?
-
-
no degradation of ICAM-3
-
-
-
additional information
?
-
-
extracellular gingipain protease activities cause a lack of secondary cytokine response in human cells after challenge with live Porphyromonas gingivalis
-
-
-
additional information
?
-
-
gingipains are cysteine proteinases and virulence factors of Porphyromonas gingivalis, the major causative bacterium of periodontal disease. Gingipains stimulate interleukin-8 secretion from human THP-1 cells, which is completely inhibited by proteinase inhibitors of gingipain and is increased in the presence of pathogen-associated molecular patterns, PAMPs, overview
-
-
-
additional information
?
-
-
gingipains are involved in bacterial adherence to host cells, RgpA binds to adhesin via its adhesin binding domain. Peptide A44 derived from the adhesin domain of RgpA plays a role in binding of Porphyromonas gingivalis to HEP-2 epithelial cells via cell surface receptors, e.g. clathrin, nocodazole and paclitaxel, which disrupt microtubule formation, block the interaction, while genistein does not
-
-
-
additional information
?
-
-
gingipains are key virulence determinants of Porphyromonas gingivalis and play a crucial role in pathogenicity
-
-
-
additional information
?
-
-
gingipains reduce cyclin expression and cause early G1 arrest, leading to the inhibition of cellular proliferation in murine ST2 osteoblastic/stromal cells, overview
-
-
-
additional information
?
-
-
HRgpA-mediated downregulation and RgpB-mediated upregulation of production of interleukin-8, occurs through protease-activated receptors, PAR-1 and PAR-2, signalling, RgpB-mediated upregulation of IL-8 production occurs through nuclear factor-kappa B, which does not affect HRgpA-mediated downregulation, overview. Gingipains preferentially suppress IL-8, resulting in attenuation of the cellular recognition of bacteria, and as a consequence, sustain chronic inflammation
-
-
-
additional information
?
-
Porphyromonas gingivalis HG66
-
gingipains cleave a broad range of in-host proteins and are key virulence factors in the onset and development of human adult periodontitis, the enzyme stimulates production of hepatocyte growth factor, i.e. scatter factor, through protease-activated receptors in human gingival fibroblasts in culture, overview
-
-
-
additional information
?
-
Porphyromonas gingivalis HG66
-
gingipains are essential for bacterial virulence and survival
-
-
-
additional information
?
-
Porphyromonas gingivalis HG66
-
HRgpA-mediated downregulation and RgpB-mediated upregulation of production of interleukin-8, occurs through protease-activated receptors, PAR-1 and PAR-2, signalling, RgpB-mediated upregulation of IL-8 production occurs through nuclear factor-kappa B, which does not affect HRgpA-mediated downregulation, overview. Gingipains preferentially suppress IL-8, resulting in attenuation of the cellular recognition of bacteria, and as a consequence, sustain chronic inflammation
-
-
-
additional information
?
-
Porphyromonas gingivalis ATCC33277
-
enzyme disrupts interaction between fibronectin and integrin in human fibroblasts, leading to cell death of detached fibroblasts, which contributes to the tissue damage in periodontal disease caused by Porphyromonas gingivalis
-
?
additional information
?
-
Porphyromonas gingivalis ATCC33277
-
gingipains reduce cyclin expression and cause early G1 arrest, leading to the inhibition of cellular proliferation in murine ST2 osteoblastic/stromal cells, overview
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
may play a role in enzyme catalysis
Ca2+
P95493, -, Q51844
stabilizes the activity
Ca2+
-
activation of prothrombin cleavage in presence of phospholipids by HRgpA not RgpB
Zn2+
-
enhances the inhibtiroy effect of chlorhexidine
Ca2+
-
stabilizes all forms of gingipain R, not necessary for activity
additional information
-
enzyme forms are not affected by Mg2+ and Ca2+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
alpha2-Macroglobulin
-
-
-
antipain
-
both enzyme forms
benzamidine derivatives
-
overview, derivatives with an urea moiety linking the 2 aromatic rings, and derivatives with a less polar ether linker, the latter being less efficient inhibitors
bis-benzamidine with urea linker
-
; best inhibitor
bovine pancreatic secretory trypsin inhibitor
-
i.e. PSTI bovine, about 33% inhibition at 0.0005 mM, 66% at 0.001 mM, and 87% at 0.0025 mM, a Kazal-type serine proteinase inhibitor purified from pancreas, bovine pancreatic secretory trypsin inhibitor having an essential Arg residue at the P1 position of the reactive site, and containing Tyr and Asn residues the P2' and P3' sites, specifically inhibits the activity of the Arg-specific gingipain R, whereas porcine inhibitor, possessing a Lys residue at the P1 position, exhibits activity only against the Lys-specific cysteine proteinase gingipain K, EC 3.4.22.47. The inhibitory effect is eliminated by Arg residue modification in 0.2 M borate buffer, pH 9.0, and 50 mM excess of cyclohexanedione in a 1 : 30 molar ratio at 37C. The association equilibrium constant is 0.0016 mM
-
carbobenzoxy-Glu(NHN(CH3)Ph)-Lys-CO-NHCH2Ph
-
-
carbobenzoxy-Lys-Arg-CO-Lys-N(CH3)2
-
i.e. KYT-1, specific inhibition of Rgp, inhibits coaggregation of Porphyromonas gingivalis with other bacteria in vivo
carbobenzoxy-Lys-Arg-CO-Lys-N-(CH3)2
-
-
chicken ovoinhibitor
-
III and IV domains having Leu and Ser or Leu and Leu, respectively, at the P2' and P3' sites
-
Chlorhexidine
-
strong inhibition
Chlorhexidine
-
synergistic effect of Zn2+ in a 1:1 ratio of chlorhexidine and Zn2+
Chloromethyl ketones
-
development of several inhibitor derivatives: structure-based design, chemistry, and activity, specificity for the Sn binding pocket of the enzyme, overview
Chloromethylketones
-
-
Collagen type I
-
fibronectin and type I collagen addition inhibited the disruptive activity of the enzyme in human fibroblasts
-
D-Arginine
-
complete inhibition of coaggregation of Porphyromonas gingivalis with other oral bacteria by L- and D-arginine
D-Phe-Phe-Arg-chloromethane
-
irreversible, strong inhibition
D-Phe-Phe-Arg-chloromethylketone
-
fast acting, irreversible alkylating inhibitor
D-Phe-Pro-Arg-chloromethane
-
irreversible, strong inhibition
D-Phe-Pro-Arg-chloromethyl ketone
-
Porphyromonas gingivalis treated with gingipain inhibitor do not induce buccal edema and gingivitis in BALB/c or C57BL/6 mice
doxycyclin
-
uncompetitive
doxycycline
-
strong inhibition
E64
-
reversible, competitive inhibition
EDTA
-
completely reversed by addition of excess Ca2+
EDTA
-
both enzyme forms
EGTA
-
completely reversed by addition of excess Ca2+
Fibronectin
-
fibronectin and type I collagen addition inhibited the disruptive activity of the enzyme in human fibroblasts
-
Hemoglobin
-
prevents haptoglobin alpha-chain degradation in serum
-
iodoacetamide
-
irreversible inhibition
iodoacetic acid
-
irreversible inhibition
kappa-casein
-
inhibits proteolytic activity associated with Porphyromonas gingivalis whole cells, purified RgpA-Kgp proteinase-adhesin complexes, and purified RgpB proteinase. The peptide kappa-casein(109-137) exhibits synergism with Zn(II) against both Arg- and Lys-specific proteinases. Active region for inhibition is identified as kappa-casein (117-137). Kappa-casein inhibits in an uncompetitive manner
-
KYT-1
-
specific Rgp inhibitor
KYT-1
-
specific inhibitor
L-arginine
-
complete inhibition of coaggregation of Porphyromonas gingivalis with other oral bacteria by L- and D-arginine
L-trans-epoxy-succinylleucylamido-(4-guanidino)butane
-
both enzyme forms
Lactoferrin
-
inhibits both the Arg- and Lys-specific proteinase activities of Porphyromonas gingivalis whole cells by approximately 40% at 1 mg/ml and over 70% at 10 mg/ml. Lactoferrin inhibits both the Arg-specific and Lys-specific activities of purified Porphyromonas gingivalis 248 RgpA/Kgp proteinase-adhesin complexes by 96% at a concentration of 5 mg/mL; lactoferrin is incubated with purified RgpB which lacks the adhesin domains of RgA and Kgp. Lactoferrin inhibits RgpB activity by 77% at a concentration of 1.0 mg/ml and by 95% at 10 mg/ml confirming the inhibition is independent of adhesins
-
Leupeptin
-
both enzyme forms
Leupeptin
-
strong inhibition
Leupeptin
-
inhibits Arg-specific Rgp, but not Lys-specific Kgp
Leupeptin
-
a specific arginine-gingipain inhibitor
Leupeptin
-
human gingvial epithelial cells treated with Rgp-specific inhibitor leupeptin and challenged with Porphyromonas gingivalis cells do not undergo apoptosis
N-alpha-tosyl-L-lysyl chloromethyl ketone
-
TLCK
N-alpha-tosyl-L-lysyl chloromethyl ketone
-
-
N-Chlorosuccinimide
-
-
N-ethylmaleimide
-
both enzyme forms
N-ethylmaleimide
-
irreversible inhibition
Nalpha-p-tosyl-L-lysine chloromethyl ketone
-
TLCK
p-aminobenzamidine
-
-
p-hydroxymercuribenzoate
-
complete inhibition at 0.2 mM, both enzyme forms
Phe-Pro-Arg-chloroethyl ketone
-
FPR-cmk, inhibits Rgps
Phe-Pro-Arg-chloromethyl ketone
-
i.e. FPR-cmk, a specific inhibitor of Rgps, the inhibitor almost completely negates the RgpB-induced upregulation and HRgpA-induced downregulation
Phe-Pro-Arg-chloromethylketone
-
-
Pro-Phe-Arg-chloromethylketone
-
-
rice grain extract
-
a rice protein fraction is shown to have Rgp inhibitory activities. Comprehensive affinity chromatography and MS analyses results in the identification of 4 proteins a 26 kDa globulin, a plant lipid transfer/trypsin-alpha amylase inhibitor, the RA17 seed allergen, and an alpha amylase/trypsin inhibitor proteins accounting for 90% of the inhibitory activity. Inhibitory activity against Rgp is 20fold higher than that against Kgp
-
tetracyclin
-
uncompetitive
tosyl-L-Lys chloromethyl ketone
-
i.e. TLCK
tosyl-L-lysine chloromethyl ketone
-
i.e. TLCK, both enzyme forms
tosyl-L-Phe chloromethyl ketone
-
i.e. TPCK
Zn2+
-
complete inhibition of both enzyme forms at 6.7 mM, increases inhibitory effect of benzamidine derivatives 2-3fold, lowers Ki-values, binding mechanism
additional information
-
resistant to inhibition by proteinase inhibitors in human plasma
-
additional information
-
no inhibition by aprotinin, epsilon-aminocaproic acid and diisopropylfluorophosphate
-
additional information
-
enzyme activity and cleavage pattern are not affected by 0.1% SDS, 1% Triton X-100, 1% octyl- and decylpyranoside
-
additional information
-
no or nearly no inhibition by cathepsin B inhibior II, metronidazole, peicillin G, and erythromycin
-
additional information
-
RgpB is stable to denaturing agents, e.g. urea, SDS, Triton X-100, and 1% octyl or decylpyranoside
-
additional information
-
gingipains stimulate interleukin-8 secretion from human THP-1 cells, which is completely inhibited by proteinase inhibitors of gingipain and is increased in the presence of pathogen-associated molecular patterns, PAMPs, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
-
2-mercaptoethanol
P95493, -, Q51844
weak activation, a concentration above 100 mM is required
cysteamine
P95493, -, Q51844
activates, best above 5 mM
cysteine
-
required for full amidolytic activity
cysteine
-
active in presence of
cysteine
P95493, -, Q51844
10 mM, most effective reducing agent for activation of the enzyme, denaturation occurs at higher concentration above 5 mM
cysteine
-
gingipains are activated by diluting to 10 mM in 0.2 M HEPES, pH 8.0, 5 mM CaCl2 and 10 mM cysteine, and incubation at 37C for 10 min
dithiothreitol
-
activates
dithiothreitol
P95493, -, Q51844
weak activation, a concentration above 100 mM is required
glutathione
P95493, -, Q51844
activates, best above 5 mM
glycyl-glycine
-
activates only RGP-B
glycyl-glycine
-
increases the substrate hydrolysis, increases Km and kcat value
glycyl-glycine
P95493, -, Q51844
stimulates the amidolytic activity and limited proteolysis, but destabilizes the enzyme; stimulates the amidolytic activity and limited proteolysis, but destabilizes the isozymes
Glycylglycine
-
stimulates depending on the substrate
Phospholipids
-
activation of prothrombin cleavage in presence of Ca2+ by HRgpA not RgpB, 1.5fold at 0.04 mg/ml
Urea
-
3fold activation at 6 M, probably due to unfolding of the substrate azocasein, which enhances the enzymes sensitivity for proteolytic cleavage
additional information
-
human serum minimal medium induces enzyme expression
-
additional information
-
enzyme activity and cleavage pattern are not affected by 0.1% SDS, 1% Triton X-100, or 1% octyl- and decylpyranoside
-
additional information
-
gingipains stimulate interleukin-8 secretion from human THP-1 cells, which is completely inhibited by proteinase inhibitors of gingipain and is increased in the presence of pathogen-associated molecular patterns, PAMPs, overview. Synergistic effects of gingipains and, synthetic TLR or NOD ligands on secretion of proinflammatory cytokines in cultured human peripheral blood mononuclear cellshuman peripheral blood mononuclear cells
-
additional information
-
activation of gingipain R by incubation for 10 min in 200 mM Tris-HCl buffer, pH 7.6, containing 50 mM Gly-Gly, 10 mM CaCl2 and 10 mM Cys-HCl
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00026
-
Prothrombin
-
HRgpA, pH 7.6, 37C, in presence of Ca2+ and phospholipids
-
0.0066
-
Prothrombin
-
RgpB, pH 7.6, 37C, in presence of Ca2+ and phospholipids
-
additional information
-
additional information
P95493, -, Q51844
-
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.076
-
Prothrombin
-
RgpB, pH 7.6, 37C, in presence of Ca2+ and phospholipids
-
0.32
-
Prothrombin
-
HRgpA, pH 7.6, 37C, in presence of Ca2+ and phospholipids
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.013
-
bis-benzamidine with urea linker
-
pH 7.6, RgpB, in presence of Zn2+
0.015
-
bis-benzamidine with urea linker
-
pH 7.6, HRgpA, in presence of Zn2+
0.03
-
bis-benzamidine with urea linker
-
pH 7.6, HRgpA and RgpB, in absence of Zn2+
0.0015
0.0022
E64
-
-
0.005
-
Lactoferrin
-
pH 8.0, 37C, a kinetic analysis of the inhibition of Arg-specific proteolytic activity of purified gingivalis RgpA/Kgp proteinase-adhesin complexes by lactoferrin demonstrates time-dependent inhibition with a first-order inactivation rate constant (kinact) of 0.023/min
-
additional information
-
additional information
-
Ki-values for benzamidine derivatives in presence or absence of Zn2+
-
additional information
-
additional information
-
inhibition kinetics, overview
-
additional information
-
additional information
-
inhibition kinetics
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
40.8
-
P95493, -, Q51844
purified isozyme IV
41.3
-
P95493, -, Q51844
purified isozyme I
42.9
-
P95493, -, Q51844
purified isozyme III
45.5
-
P95493, -, Q51844
purified isozyme II
additional information
-
-
-
additional information
-
-
activity induction in bacterial culture
additional information
-
-
-
additional information
-
-
quantification of hepatocyte growth factor induction by RgpB and HRgpA
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
assay at
7.5
8
-
both enzyme forms
7.5
-
-
in presence of glycylglycine
7.5
-
P95493, -, Q51844
protein substrates
7.6
8.3
-
assay at
8
-
P95493, -, Q51844
4-nitroanilide substrates
8
-
-
coaggregation assay at
8
-
P28784, P95493
assay at; assay at
8.1
-
-
assay at
9.5
-
P95493, -, Q51844
protein substrates
9.5
-
-
substrate Bz-L-Arg-nitroanilide
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
9.5
P95493, -, Q51844
50% activity at pH 5.0, maximal activity at pH 9.5
5
9.5
-
50% of maximal activity at pH 5.0
8.5
-
-
rapid decrease of activity above pH 8.5
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22
-
-
coaggregation assay at room temperature
22
-
-
assay at room temperature
37
-
-
assay at, substrate haemoglobin
37
-
P95493, -, Q51844
assay at
37
-
P28784, P95493
assay at; assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
37
-
with denatured substrate collagen type I, native collagen type I is only degraded at 37C
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3.74
-
P95493, -, Q51844
isoelectric focusing
3.8
-
-
RGP-B, isoelectric focusing
4
5
-
isoelectric focusing
4.7
4.8
-
RGP-A, isoelectric focusing
4.96
-
P95493, -, Q51844
isozyme IV, isoelectric focusing
5.03
-
P95493, -, Q51844
isozyme III, isoelectric focusing
5.09
-
P95493, -, Q51844
isozyme II, isoelectric focusing
5.1
-
-
RgpB isozyme II, isoelectric focusing
5.1
-
-
gingipain R2 isozyme II, isoelectric focusing
5.21
-
P95493, -, Q51844
isozyme I, isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
attached to the cell surface
-
Manually annotated by BRENDA team
P95493, -, Q51844
secretion
-
Manually annotated by BRENDA team
-
the enzyme is secreted
-
Manually annotated by BRENDA team
-
in extracellular vesicles and soluble in the culture supernatant
-
Manually annotated by BRENDA team
Porphyromonas gingivalis A7436
-
-
-
-
Manually annotated by BRENDA team
Porphyromonas gingivalis ATCC33277
-
; attached to the cell surface; secretion
-
-
Manually annotated by BRENDA team
Porphyromonas gingivalis HG66
-
the enzyme is secreted
-
-
Manually annotated by BRENDA team
-
associated to the outer membrane and vesicles
Manually annotated by BRENDA team
-
outer membrane attached
Manually annotated by BRENDA team
-
outer membrane protein Sov participates in the secretion of Arg-gingipain. Secretion is Rgp inhibited by anti-Sov antiserum raised against the C-terminal region of Soc
Manually annotated by BRENDA team
-
Porphyromonas gingivalis secretes outer membrane vesicles that contain major virulence factors, including Arg-gingipain and Lys-gingipain
Manually annotated by BRENDA team
additional information
-
localization pattern in strain FLL203 is affected upon cell growth at 42C
-
Manually annotated by BRENDA team
additional information
-
gingipain adhesin domains are involved in targeting their associated proteolytic activities to cell surface receptors, colocalization of the arg-gingipain, RgpA, adhesin domain with fibronectin and the alpha5beta1 integrin receptor for fibronectin
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Porphyromonas gingivalis (strain ATCC BAA-308 / W83)
Porphyromonas gingivalis (strain ATCC BAA-308 / W83)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
44000
-
-
Porphyromonas gingivalis, gel filtration
45000
-
-
Porphyromonas gingivalis
48120
48150
P95493, -, Q51844
mature, C-terminally truncated isozymes, amino acid sequence calculation and mass spectroscopy; mature, C-terminally truncated isozymes, amino acid sequence calculation, gel filtration and mass spectroscopy
50000
-
-
RgpB, gel filtration
50000
-
-
SDS-PAGE
55000
-
-
Porphyromonas gingivalis, enzyme form Arg-gingivain-55
70000
-
-
Porphyromonas gingivalis, enzyme form Arg-gingivain-70
75000
-
-
Porphyromonas gingivalis, enzyme form Arg-gingivain-75
95000
-
P95493, -, Q51844
a complex of catalytic and hemagglutinin/adhesin domains, gel filtration
95000
-
-
HRgpA, gel filtration
additional information
-
-
the enzyme exists as multiple MW species. The major forms are: 110000 MW, 95000 MW, 70000-90000 MW, and 50000 MW. The first two being a complex of the 50000 MW catalytic subunit with hemagglutinins, with or without an added membrane anchorage peptide. The other forms are single-chain enzymes. The 95000 MW and the 50000 MW form are found predominantly in culture medium, the 110000 and 70000-90000 MW foms are associated with membranous fractions of the bacteria
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
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x * 43000, both enzyme forms, SDS-PAGE
?
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native and C244A mutant enzyme expressed with numerous bands, 80000-9000 Da, SDS-PAGE; truncated enzyme expressed as 71000 Da and 48000 Da isoforms, SDS-PAGE; x * 56000, RgpB, calculated from the deduced amino acid sequence
dimer
-
heterodimeric RgpA fused to adhesin, i.e. HRgpA
dimer
-
heterodimer, HRgpA
dimer
Porphyromonas gingivalis HG66
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heterodimer, HRgpA
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monomer
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1 * 50000, Porphyromonas gingivalis, SDS-PAGE
monomer
P95493, -, Q51844
1 * 48019-48369, gingipain R2 isozymes I-IV and laser mass spectroscopy; 1 * 48019-48369, gingipain R2 isozymes I-IV, laser mass spectroscopy
monomer
-
1 * 48000, RgpB, SDS-PAGE
monomer
Porphyromonas gingivalis HG66
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1 * 48000, RgpB, SDS-PAGE; 1 * 48019-48369, gingipain R2 isozymes I-IV and laser mass spectroscopy; 1 * 48019-48369, gingipain R2 isozymes I-IV, laser mass spectroscopy
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additional information
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molecular modeling of the catalytic domain structure of HRgpA based on the RgpB structure, isoforms HRgpA and RgpB, the first containing 4 amino acid changes compared to the latter, which are D281N, Y283S, P286S, and N331K that all map to the region surrounding the active site
additional information
P95493, -, Q51844
the enzyme complex consists of 4 major polypeptides of 49.5 kDa for the catalytic domain, 43 kDa, 23.3 kDa, and 15.9 kDa
additional information
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Rgp possesses C-terminal a hemagglutinin domain containing the proteins responsible for coaggregation activity of Porphyromonas gingivalis, overview
additional information
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structure analysis, gingipain R occurs in different forms of 50-110 kDa, tertiary structure, the C-terminus shows an IgSF-like fold, overview
additional information
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RgpA and Kgp proteinase polyprotein domain structure, peptide mass fingerprinting and mass spectrometry, overview
additional information
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crystal structure analysis
additional information
-
RgpA can occur as monomer or as heterodimer fused to adhesins and a hemagglutinin domain, while RgpB possesses only a small hemagglutinin domain, domain structure, overview
additional information
-
RgpA possesses an adhesin domain
additional information
-
x * 95000, HRgpA, SDS-PAGE, 50000, RgpB, SDS-PAGE
additional information
Porphyromonas gingivalis HG66
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crystal structure analysis; the enzyme complex consists of 4 major polypeptides of 49.5 kDa for the catalytic domain, 43 kDa, 23.3 kDa, and 15.9 kDa; x * 95000, HRgpA, SDS-PAGE, 50000, RgpB, SDS-PAGE
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additional information
Porphyromonas gingivalis RgpA
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RgpA and Kgp proteinase polyprotein domain structure, peptide mass fingerprinting and mass spectrometry, overview
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
glycoprotein
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monosaccharide composition of RgpA, expression of RgpB is required for correct glycosylation and stability of monomeric RgpA from strain W50
proteolytic modification
P95493, -, Q51844
the mature enzyme is C-terminally truncated to 433 amino acid residues
proteolytic modification
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gingipain R performs autoprocessing and activation to mature enzyme, overview
proteolytic modification
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RgpA and Kgp proteinases are synthesized as a polyprotein and proteolytically processed to individual proteinases and adhesins, C-terminal processing by carboxypeptidase CPG70
proteolytic modification
Porphyromonas gingivalis ATCC33277
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the mature enzyme is C-terminally truncated to 433 amino acid residues
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proteolytic modification
Porphyromonas gingivalis RgpA
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RgpA and Kgp proteinases are synthesized as a polyprotein and proteolytically processed to individual proteinases and adhesins, C-terminal processing by carboxypeptidase CPG70
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Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
purified enzyme gingipain R2 in complex with fast acting, irreversible inhibitor H-D-Phe-Phe-Arg-chloromethylketone, activated by incubation for 30 min in 0.1 M HEPES, pH 8.0, 10 mM L-cysteine, 2.5 mM CaCl2, at 37C, alkylation of the active site cysteine by addition of inhibitor, crystallization by sitting-drop vapour diffusion method at 20C, different protein-inhibitor complex solution systems using PEG 8000 as precipitant for 10 mg/ml protein, X-ray diffraction structure determination at 2.9 A resolution and analysis
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purified RgpB free or in complex with fast acting, irreversible inhibitor D-Phe-Phe-Arg-chloromethylketone, activated by incubation for 30 min in 0.1 M HEPES, pH 8.0, 10 mM L-cysteine, 2.5 mM CaCl2, at 37C, alkylation of the active site cysteine by addition of inhibitor, crystallization of dialysed sample by vapour diffusion method, 8 mg/ml protein in 3 mM MOPS, pH 7.2 0.02% NaN3, plus equal volume of reservoir solution: 3.4 M 1,6-hexandiol, 0.2 M MgCl2, 0.1 M Tris-HCl, pH 8.5, at 21C, several weeks, X-ray diffraction structure determination at 1.5-2.16 A resolution and analysis, structure modeling
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pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.8
8.3
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stability of RgpA catalytic domain of wild-type and D7 mutant strain at 30C in absence or presence of 2-mercaptoethanol or Ca2+, overview
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
45
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50 mM Tris,-HCl, pH 7.8, 10 min, remaining activity for RGP-A is 82% and for RGP-B 52% of maximal activity, after 30 min remaining activity for RGP-A is 58% and for RGP-B 26% of maximal activity
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
1% SDS slightly decreases enzyme activity
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Ca2+ stabilizes
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Ca2+ stabilizes all forms of gingipain R
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Ca2+ stabilizes the enzyme, while glycyl-glycine destabilizes the enzyme
P95493, -, Q51844
Ca2+ stabilizes the isozymes, while glycyl-glycine destabilizes the isozymes
P95493, -, Q51844
enzyme is completely inactivated in 8 M urea
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expression of RgpB is required for correct glycosylation and stability of monomeric RgpA from strain W50
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Irreversible loss of activity during lyophilization
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RgpB is stable and active in buffers containing 6 M urea, 0.1% SDS, 1% Triton X-100, and 1% octyl or decylpyranoside
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RgpB is stable to denaturing agents, e.g. urea, SDS, Triton X-100, and 1% octyl or decylpyranoside
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STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, buffer with neutral pH, 1-5 mM CaCl2, indefinitely stable
P95493, -, Q51844
-20C, stable for several months
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0C, on ice, buffer with neutral pH, 1-5 mM CaCl2, stable for months
P95493, -, Q51844
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
enzyme form Arg-gingivain-75, Arg-gingivain-70 and Arg-gingivain-55
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from cell culture medium; isozymes I-IV from cell culture medium, 4.5-5fold
P95493, -, Q51844
native enzyme from envelope and/or outer membranes by ammonium sulfate or acetone precipitation, ion exchange chromatography, gel filtration, isoelectric or chromatofocusing, and affinity chromatography
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native enzymes by ammonium sulfate fractionation, ion exchange and affinity chromatography, RgpA and RgpB by different methods, overview
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native extracellular enzyme from culture medium
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native HRgpA and RgpB
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native HRgpA and RgpB from culture supernatant
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recombinant protein using His-tag
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RGP-A and RGP-B, from envelope material, solubilization by detergent 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate, i.e. CHAPS
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using affinity and ion exchange chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
different enzyme fragments expressed as His-tag fusion proteins in Escherichia coli BL21(DE3)
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expression of wild-type and mutant enzymes in murine ST2 osteoblastic/stromal cells
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gene rgpA, expression analysis and regulation
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initial translation products, overview
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RgpB as a full-length zymogen, with a catalytic Cys244Ala mutation, or with the C-terminal 72 amino acids deleted in an Arg-gingipain Porphyromonas gingivalis mutant (YH522AB) and an Arg- and Lys-gingipain mutant (YH522KAB)
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RgpB with the C-terminal His-tag is produced by the Porphyromonas gingivalis W83 strain bearing the modified rgpB gene
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ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C244A
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mature enzyme numbering, inactive, correct localization
DELTA435-507
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largely inactive, incorrect localization in culture supernatant and periplasm
additional information
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4 naturally occuring enzyme deficient mutants: rgpA-deficient mutant shows 77% activity compared to the wild-type activity with type I collagen, while a rgpB-deficent mutant shows 82% activity, and a double-deficient mutant strain shows only 6% activity, another mutant lacking the to arginine-specific isozyme and the lysine-specific gingipain KGP shows 5% remaining activity
additional information
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strain W501 is deficient for RgpA, strain E8 for Rgp, and strain D7 for RgpB
additional information
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mutant RgpA-deficient isogenic strain W501 and RgpB-deficient isogenic strain D7 show 50% of wild-type strain W50 enzyme activity
additional information
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Rgp null mutant strain KDP133 shows platelet aggregation similar to the wild-type strain ATCC 33277, while neither the Rgp/Kgp null mutant strain, nor the adhesin null mutant strain show platelet aggregation
additional information
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construction of a strain producing Kgp proteinase without the adhesin domains in a Rgp/Kgp/adhesin-null mutant, mutant strains 33277, KDP133, and KDP137 phenotypes, overview
additional information
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construction of enzyme-deficient mutants KDP136 with DELTArgpADELTArgpBDELTAkgp, and KDP133 with DELTAkgp. The mutants do not, in contrast to the wild-type enzyme, inhibit cellular proliferation and don not arrest the cell cycle in the G0/G1 phase as well as decrease the expression levels of the cell-cycle regulatory molecules cyclin D and cyclin E in murine ST2 cells, overview
additional information
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gingipain-deficient Porphyromonas gingivalis mutants lacking both Arg- and Lys-gingipains are unable to induce interleukin-1beta, interleukin-6, and interleukin-8 degradation
additional information
Porphyromonas gingivalis ATCC33277
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4 naturally occuring enzyme deficient mutants: rgpA-deficient mutant shows 77% activity compared to the wild-type activity with type I collagen, while a rgpB-deficent mutant shows 82% activity, and a double-deficient mutant strain shows only 6% activity, another mutant lacking the to arginine-specific isozyme and the lysine-specific gingipain KGP shows 5% remaining activity; construction of enzyme-deficient mutants KDP136 with DELTArgpADELTArgpBDELTAkgp, and KDP133 with DELTAkgp. The mutants do not, in contrast to the wild-type enzyme, inhibit cellular proliferation and don not arrest the cell cycle in the G0/G1 phase as well as decrease the expression levels of the cell-cycle regulatory molecules cyclin D and cyclin E in murine ST2 cells, overview
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additional information
Porphyromonas gingivalis HG66
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construction of a strain producing Kgp proteinase without the adhesin domains in a Rgp/Kgp/adhesin-null mutant, mutant strains 33277, KDP133, and KDP137 phenotypes, overview
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Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
pretreatment with a reducing agent required for activity
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APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
biotechnology
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a naive camel nanobody library is constructed and phage display is used to select one nanobody toward RgpB with picomolar affinity. The nanobody is highly specific for RgpB given that it does not bind to the homologous gingipain HRgpA, indicating the presence of a binding epitope within the immunoglobulin-like domain of RgpB. RgpB can be used as a specific biomarker for Porphyromonas gingivalis infection
diagnostics
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the enzyme activity is used for detection of periodontitis at an early stage of the disease
drug development
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potential target for the development of an anti-periodontitis vaccination
medicine
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development of structure-based inhibitors for treatment of periodontal diseases
medicine
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development of potent, gingipain-specific inhibitors might be a helpful tool in a therapeutic strategy to prevent or treat periodontal disease
molecular biology
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enzyme is a convenient tool for protein chemistry due to its stability and activity under conditions of high detergent concentration used in protein solubilization and purification
pharmacology
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enzyme structure is an excellent template for the rational design of drugs with a potential to cure and prevent periodontitis
medicine
Porphyromonas gingivalis HG66
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development of structure-based inhibitors for treatment of periodontal diseases
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pharmacology
Porphyromonas gingivalis HG66
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enzyme structure is an excellent template for the rational design of drugs with a potential to cure and prevent periodontitis
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