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Information on EC 3.4.22.37 - gingipain R and Organism(s) Porphyromonas gingivalis and UniProt Accession P28784
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3.4.22.37 gingipain RSpecify your search results
Word Map
- 3.4.22.37
- porphyromonas
- gingivalis
- periodontal
- proteinases
- adhesins
-
lysine-specific
- hemagglutinins
-
hemagglutination
-
protease-activated
-
keystone
-
periodontopathogenic
-
fimbriae
-
crevicular
- diagnostics
- actinomycetemcomitans
- biotechnology
- molecular biology
- forsythia
- johnsoniae
-
periodontopathic
-
gingivalis-induced
-
black-pigmented
- par-2
-
subgingival
-
peptidylarginine
-
tooth-supporting
-
tannerella
-
gliding
-
autoaggregation
- medicine
- pharmacology
- drug development
-
lys-specific
The taxonomic range for the selected organisms is: Porphyromonas gingivalis
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
hydrolysis of proteins and small molecule substrates, with a preference for Arg in P1
Synonyms
gingipain, arg-gingipain, hrgpa, rgp-1, gingipain r, gingipain-r, arginine-specific cysteine proteinase, gingipain r1, arginine-specific gingipain, arg-gingipain a, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
HRgpA
Arg-gingipain
Arg-gingivain-55 proteinase
-
-
-
-
Arg-gingivain-70 proteinase
-
-
-
-
Arg-gingivain-75 proteinase
-
-
-
-
Argingipain
-
-
-
-
Arginine-specific cysteine protease
arginine-specific cysteine proteinase
Arginine-specific gingipain
Arginine-specific gingivain
-
-
-
-
gingipain R2
Gingipain-1
-
-
-
-
Gingivain, arginine-specific
-
-
-
-
HRgpA
RGP
RGP-1
-
-
-
-
RGP-2
RgpA
-
-
RgpB
additional information
-
the enzyme belongs to the peptidase family C25, clan CD
Arg-gingipain
-
-
-
-
Arg-gingipain
-
-
Arg-gingipain
-
cysteine proteinases, products of the genes rgpA and rgpB
Arginine-specific cysteine protease
-
-
-
-
Arginine-specific gingipain
-
-
-
-
Arginine-specific gingipain
-
-
gingipain R2
two different enzymes gingipain R exist in Porphyromonas gingivalis, that are encoded by related but individual genes
HRgpA
-
-
HRgpA
-
high molecular weight form containing both catalytic and adhesin subunit
RGP
-
-
-
-
RGP
-
-
RgpB
-
-
RgpB
-
low molecular weight form containing only the catalytic domain and a small C-terminal segment
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hydrolysis of proteins and small molecule substrates, with a preference for Arg in P1
active site structure
-
hydrolysis of proteins and small molecule substrates, with a preference for Arg in P1
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
proteolysis of selected proteins
hydrolysis of proteins and small molecule substrates, with a preference for Arg in P1
active site structure, role of the Sn binding pocket, molecular basis for substrate specificity
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
hydrolysis of peptide bond
-
-
-
-
hydrolysis of peptide bond
-
-
CAS REGISTRY NUMBER
COMMENTARY
159745-71-8
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
elafin + H2O
?
all three gingipains have the ability to degrade elafin (endogenous inhibitor secreted by epithelial cells)
-
-
?
N-alpha-benzoyl-DL-arginine-4-nitroanilide + H2O
N-alpha-benzoyl-DL-arginine + 4-nitroaniline
-
-
-
?
alpha chains of haptoglobin + H2O
?
-
low activity, hemoglobin protects
-
?
alpha-globin + H2O
?
-
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
-
HRgpA and RgpB, cleavage of peptide bond R383-N394
-
?
alpha1-Antichymotrypsin + H2O
?
inactivation of the substrate
-
?
apoB-100 protein + H2O
?
-
apoB-100 degradation induces LDL-modification and contributes to the onset of atherosclerosis
-
-
?
AWTPTPTPLSTPSIIRTTGLRPYPSSVLI + H2O
AWTPTPTPLSTPSIIR + TTGLRPYPSSVLI
-
-
-
-
?
benzoyl-Arg 4-nitroanilide + H2O
benzoyl-Arg + 4-nitroaniline
-
-
-
-
?
benzoyl-Arg-4-nitroanilide + H2O
benzoyl-Arg + 4-nitroaniline
-
-
-
-
?
Benzoyl-Ile-Glu-(gamma-ornithyl)-Gly-Arg 4-nitroanilide + H2O
?
-
-
-
-
?
benzoyl-Phe-Val-Arg-4-nitroanilide + H2O
benzoyl-Phe-Val-Arg + 4-nitroaniline
-
-
-
?
benzoyl-Pro-Phe-Arg-4-nitroanilide + H2O
benzoyl-Pro-Phe-Arg + 4-nitroaniline
-
-
-
?
benzoyl-Val-Gly-Arg-4-nitroanilide + H2O
benzoyl-Val-Gly-Arg + 4-nitroaniline
-
-
-
?
beta-globin + H2O
?
-
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
?
-
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
-
best sythetic substrate
-
?
butoxy-carbonyl-Val-Leu-Gly-Arg-4-nitroanilide + H2O
butoxy-carbonyl-Val-Leu-Gly-Arg + 4-nitroaniline
-
-
-
?
CBZ-Phe-Arg-4-methyl-coumaryl-7-amide + H2O
CBZ-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
CD27 protein + H2O
?
-
involved in reduction of T-cell function, effective even in the presence of 2.5 or 5% serum
-
-
?
cell adhesion molecule + H2O
?
-
involved in the detachment of endothelial cells
-
-
?
Collagen type I + H2O
?
-
not the purified isoforms, enzyme probably needs to be attached to the cell surface
-
?
denatured alpha1-proteinase inhibitor + H2O
?
-
-
?
elafin + H2O
?
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
?
-
activation through limited proteolysis
-
-
?
factor X proenzyme + H2O
?
-
activation through limited proteolysis
-
-
?
fibrinogen A alpha-chain + H2O
28 kDa fragment + ?
-
major cleavage site at position 22, all isoforms
the 28 kDa fragment is the major product of isoform HRgpA
?
fibrinogen B beta-chain + H2O
?
-
high activity of isoform HRgpA, which performs cleavage at 2 positions: 42 and 44
-
?
Fibronectin + H2O
?
-
the enzyme isoforms HRgpA and RgpB effectively destroy the cell-binding domain of fibronectin
-
-
?
haemoglobin + H2O
?
-
complete digestion, enzyme form RGP-B shows high activity, not RGP-A, human substrate
-
?
hemopexin + H2O
hemin + ?
-
-
products of 23 kDa and 47 kDa, products of 23 kDa and 40 kDa in serum
?
Leu-Tyr-Arg-4-nitroanilide + H2O
Leu-Tyr-Arg + 4-nitroaniline
synthetic fluorogenic substrate
-
?
Lysozyme + H2O
?
-
absolutely specific cleavage of all Arg-Xaa peptides bonds
-
?
N-alpha-benzoyl-D,L-arginine-4-nitroanilide + H2O
N-alpha-benzoyl-L-arginine + 4-nitroaniline
-
-
-
-
?
N-alpha-benzoyl-DL-Arg-4-nitroanilide + H2O
N-alpha-benzoyl-DL-Arg + 4-nitroaniline
-
-
-
-
?
N-alpha-benzoyl-DL-arginine 4-nitroanilide + H2O
N-alpha-benzoyl-DL-arginine + 4-nitroaniline
-
-
-
-
?
N-alpha-benzoyl-DL-arginine-4-nitroanilide + H2O
N-alpha-benzoyl-DL-arginine + 4-nitroaniline
N-alpha-benzoyl-DL-Lys-4-nitroanilide + H2O
N-alpha-benzoyl-DL-Lys + 4-nitroaniline
-
-
-
-
?
N-alpha-benzoyl-L-arginine-4-nitroanilide + H2O
N-alpha-benzoyl-L-arginine + 4-nitroaniline
-
-
-
-
?
N-benzoyl-L-arginine-4-nitroanilide + H2O
N-benzoyl-L-arginine + 4-nitroaniline
-
-
-
?
N-cadherin + H2O
?
-
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
-
-
-
-
?
Nalpha-benzoyl-D,L-Arg-4-nitroanilide + H2O
Nalpha-benzoyl-D,L-Arg + 4-nitroaniline
-
-
-
-
?
Nalpha-benzoyl-D,L-arginine 4 nitroanilide + H2O
Nalpha-benzoyl-D,L-arginine + 4 nitroaniline
-
-
-
-
?
Nalpha-benzoyl-L-Arg-4-nitroanilide + H2O
Nalpha-benzoyl-L-Arg + 4-nitroaniline
-
-
-
-
?
Nalpha-benzoyl-L-arginine 4-nitroanilide + H2O
Nalpha-benzoyl-L-arginine + 4-nitroaniline
-
-
-
-
?
oxyhaemoglobin + H2O
methaemoglobin
-
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 + ?
-
data indicate direct product formation without the occurrence of intermediates
-
-
?
prefimbrillin + H2O
fimbrilline + ?
-
-
mature form of the protein
-
?
protease-activated receptor-1 + H2O
?
-
specific substrate for Arg-gingipain
-
-
?
prothrombin + H2O
alpha-thrombin + 2 peptide fragments
-
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
-
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
thrombin + ?
-
HRgpA, involved in fibrinogen clotting
-
?
RgpA-HagA polyprotein + H2O
?
-
processing of the precursor by Rgp
-
-
?
ribonuclease A + H2O
?
-
absolutely specific cleavage of all Arg-Xaa peptides bonds
-
?
t-butyloxycarbonyl-L-leucylglycyl-L-arginine-4-metylcoumaryl-7-amide + H2O
?
-
-
-
-
?
thrombomodulin + H2O
?
-
Lys-gingipain and Arg-gingipain cleave thrombomodulin in vitro
-
-
?
toluenesulfonyl-glycyl-L-prolyl-L-arginine-4-nitroanilide + H2O
toluenesulfonyl-glycyl-L-prolyl-L-arginine + 4-nitroaniline
-
-
-
?
tosyl-Gly-L-Pro-L-Arg 4-nitroanilide + H2O
tosyl-Gly-L-Pro-L-Arg 4-nitroaniline
-
-
-
-
?
tosyl-GPR-4-nitroanilide + H2O
tosyl-GPR + 4-nitroaniline
other substrates with a Ps proline are very poor substrates, synthetic fluorogenic substrate
-
?
transferring receptor + H2O
?
-
Rgp is responsible for transferring receptor degradation
-
-
?
Z-Arg-7-amido-4-methylcoumarin + H2O
Z-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
Z-Arg-Arg-4-nitroanilide + H2O
Z-Arg-Arg + 4-nitroaniline
synthetic fluorogenic substrate
-
?
azocasein + H2O
?
synthetic chromogenic substrate
-
?
benzoyl-L-arginine-4-nitroanilide + H2O
benzoyl-L-arginine + 4-nitroaniline
-
-
-
?
benzoyl-L-arginine-4-nitroanilide + H2O
benzoyl-L-arginine + 4-nitroaniline
-
-
-
-
?
benzoyl-L-arginine-4-nitroanilide + H2O
benzoyl-L-arginine + 4-nitroaniline
synthetic fluorogenic substrate
-
?
human protease-activated receptor PAR-1 + H2O
?
-
PAR-1 activation on epithelial cells
-
-
?
human protease-activated receptor PAR-2 + H2O
?
-
PAR-2 activation on epithelial cells
-
-
?
interferon gamma + H2O
?
-
degradation leading to local cytokine paralysis impairing the inflammation-dependent host defense mechanisms
-
-
?
interleukin 12 + H2O
?
-
degradation leading to local cytokine paralysis impairing the inflammation-dependent host defense mechanisms
-
-
?
interleukin-1beta + H2O
?
-
biological inactivation and degradation, low activity, cytokine degradation is mainly the result of Lys-gingipain, EC 3.4.22.47
-
-
?
interleukin-6 + H2O
?
-
biological inactivation and degradation
-
-
?
interleukin-8 + H2O
?
-
biological inactivation and degradation
-
-
?
N-alpha-benzoyl-DL-arginine-4-nitroanilide + H2O
N-alpha-benzoyl-DL-arginine + 4-nitroaniline
-
-
-
-
?
N-alpha-benzoyl-DL-arginine-4-nitroanilide + H2O
N-alpha-benzoyl-DL-arginine + 4-nitroaniline
-
-
-
?
RgpA-Hgp polyprotein + H2O
?
-
processing of the precursor by Rgp
-
-
?
RgpA-Hgp polyprotein + H2O
?
-
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
?
-
reduction of the protective effect of SLPIon neutrophil proteases and bacterial proinflammatory compounds
-
-
?
secretory leucocyte protease inhibitor + H2O
?
-
recombinant protein, reaction catalyzed by RgpA and RgpB
-
-
?
TNFalpha + H2O
?
-
degradation leading to local cytokine paralysis impairing the inflammation-dependent host defense mechanisms
-
-
?
TNFalpha + H2O
?
-
inactivation by degradation of human TNFalpha on host cell surface and recombinant fibroblast cell surface, leading to inhibition of biological functions of TNFalpha, overview
-
-
?
TNFalpha + H2O
?
-
degradation, high activity with HRgpA, moderate activity with RgpB
-
-
?
transferrin + H2O
hemin + ?
-
slight truncation of the polypeptide chain in serum
-
?
Z-Phe-Arg-7-amido-4-methylcoumarin + H2O
Z-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
Z-Phe-Arg-7-amido-4-methylcoumarin + H2O
Z-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
?
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
?
-
-
substrate specificity, no inactivation of native alpha1-proteinase inhibitor and native type I collagen
-
?
additional information
?
-
substrate specificity, no inactivation of native alpha1-proteinase inhibitor and native type I collagen
-
?
additional information
?
-
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
-
-
?
additional information
?
-
-
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
-
-
?
additional information
?
-
-
important virulence factors in periodontitis
-
-
?
additional information
?
-
-
important virulence factors in periodontitis
-
-
?
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
?
-
-
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
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
elafin + H2O
?
all three gingipains have the ability to degrade elafin (endogenous inhibitor secreted by epithelial cells)
-
-
?
apoB-100 protein + H2O
?
-
apoB-100 degradation induces LDL-modification and contributes to the onset of atherosclerosis
-
-
?
CD27 protein + H2O
?
-
involved in reduction of T-cell function, effective even in the presence of 2.5 or 5% serum
-
-
?
cell adhesion molecule + H2O
?
-
involved in the detachment of endothelial cells
-
-
?
Collagen type I + H2O
?
-
not the purified isoforms, enzyme probably needs to be attached to the cell surface
-
?
elafin + H2O
?
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
?
-
activation through limited proteolysis
-
-
?
factor X proenzyme + H2O
?
-
activation through limited proteolysis
-
-
?
Fibronectin + H2O
?
-
the enzyme isoforms HRgpA and RgpB effectively destroy the cell-binding domain of fibronectin
-
-
?
hemopexin + H2O
hemin + ?
-
-
products of 23 kDa and 40 kDa in serum
?
human protease-activated receptor PAR-1 + H2O
?
-
PAR-1 activation on epithelial cells
-
-
?
human protease-activated receptor PAR-2 + H2O
?
-
PAR-2 activation on epithelial cells
-
-
?
interferon gamma + H2O
?
-
degradation leading to local cytokine paralysis impairing the inflammation-dependent host defense mechanisms
-
-
?
interleukin 12 + H2O
?
-
degradation leading to local cytokine paralysis impairing the inflammation-dependent host defense mechanisms
-
-
?
interleukin-1beta + H2O
?
-
biological inactivation and degradation, low activity, cytokine degradation is mainly the result of Lys-gingipain, EC 3.4.22.47
-
-
?
interleukin-6 + H2O
?
-
biological inactivation and degradation
-
-
?
interleukin-8 + H2O
?
-
biological inactivation and degradation
-
-
?
oxyhaemoglobin + H2O
methaemoglobin
-
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 + ?
-
-
mature form of the protein
-
?
protease-activated receptor-1 + H2O
?
-
specific substrate for Arg-gingipain
-
-
?
prothrombin + H2O
thrombin + ?
-
HRgpA, involved in fibrinogen clotting
-
?
RgpA-HagA polyprotein + H2O
?
-
processing of the precursor by Rgp
-
-
?
RgpA-Hgp polyprotein + H2O
?
-
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
?
-
reduction of the protective effect of SLPIon neutrophil proteases and bacterial proinflammatory compounds
-
-
?
transferrin + H2O
hemin + ?
-
slight truncation of the polypeptide chain in serum
-
?
transferring receptor + H2O
?
-
Rgp is responsible for transferring receptor degradation
-
-
?
TNFalpha + H2O
?
-
degradation leading to local cytokine paralysis impairing the inflammation-dependent host defense mechanisms
-
-
?
TNFalpha + H2O
?
-
inactivation by degradation of human TNFalpha on host cell surface and recombinant fibroblast cell surface, leading to inhibition of biological functions of TNFalpha, overview
-
-
?
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
-
-
?
additional information
?
-
-
important virulence factors in periodontitis
-
-
?
additional information
?
-
-
important virulence factors in periodontitis
-
-
?
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
?
-
-
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
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
additional information
-
enzyme forms are not affected by Mg2+ and Ca2+
Ca2+
-
activation of prothrombin cleavage in presence of phospholipids by HRgpA not RgpB
Ca2+
-
stabilizes all forms of gingipain R, not necessary for activity
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
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 37°C. The association equilibrium constant is 0.0016 mM
-
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
chicken ovoinhibitor
-
III and IV domains having Leu and Ser or Leu and Leu, respectively, at the P2' and P3' sites
-
Chloromethyl ketones
-
development of several inhibitor derivatives: structure-based design, chemistry, and activity, specificity for the Sn binding pocket of the enzyme, overview
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-chloromethylketone
-
fast acting, irreversible alkylating inhibitor
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
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
-
Indocyanine green
Arg-gingipain is one of the important targets of indocyanine green as a photosensitizer
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
-
Kappaphycus alvarezii bromophenol
-
potent natural metabolite to control Porphyromas gingivalis induced infection
-
Kappaphycus alvarezii extract
-
potent natural metabolite to control Porphyromas gingivalis induced infection
-
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
p-hydroxymercuribenzoate
-
complete inhibition at 0.2 mM, both enzyme forms
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
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
-
RRLMAAKAESRK
mixed-type inhibitor, the arginine residue at position 15 of the docapeptide substantially contributes to the enzyme-inhibitory activity and the arginine residue at position 14 plays important roles in exerting enzyme-inhibitory activity
Chlorhexidine
-
synergistic effect of Zn2+ in a 1:1 ratio of chlorhexidine and Zn2+
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
-
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
-
-
leupeptin
-
human gingvial epithelial cells treated with Rgp-specific inhibitor leupeptin and challenged with Porphyromonas gingivalis cells do not undergo apoptosis
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
-
enzyme activity and cleavage pattern are not affected by 0.1% SDS, 1% Triton X-100, 1% octyl- and decylpyranoside
-
additional information
-
no inhibition by aprotinin, epsilon-aminocaproic acid and diisopropylfluorophosphate
-
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
-
additional information
-
protein extracts from polished rice inhibit the proteolytic activity of the enzyme
-
additional information
-
the prodomain of lysine-specific gingipain shows no inhibitory activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
2-mercaptoethanol
weak activation, a concentration above 100 mM is required
cysteine
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 37°C for 10 min
dithiothreitol
weak activation, a concentration above 100 mM is required
glycyl-glycine
-
increases the substrate hydrolysis, increases Km and kcat value
glycyl-glycine
stimulates the amidolytic activity and limited proteolysis, but destabilizes the enzyme
glycyl-glycine
stimulates the amidolytic activity and limited proteolysis, but destabilizes the isozymes
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
-
human serum minimal medium induces enzyme expression
-
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
-
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
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00026
prothrombin
-
HRgpA, pH 7.6, 37°C, in presence of Ca2+ and phospholipids
-
0.0066
prothrombin
-
RgpB, pH 7.6, 37°C, in presence of Ca2+ and phospholipids
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.076
prothrombin
-
RgpB, pH 7.6, 37°C, in presence of Ca2+ and phospholipids
-
0.32
prothrombin
-
HRgpA, pH 7.6, 37°C, in presence of Ca2+ and phospholipids
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0029
2,6-bis-(4-amidinobenzyl)-cyclohexanone
at pH 7.6 and 37°C
0.0029
2,6-bis-(4-amidinobenzyl)-cyclohexanone
at pH 7.6 and 37°C
0.005
lactoferrin
-
pH 8.0, 37°C, 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
-
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+
0.00000085
prodomain of arginine-specific gingipain A
-
isoform HRgpA, in 200 mM Tris-HCl, 5 mM CaCl2, 150 mM NaCl, and 0.02% (w/v) NaN3, pH 7.6, supplemented with 10 mM L-cysteine, at 37°C
-
0.0000021
prodomain of arginine-specific gingipain A
-
isoform RgpB, in 200 mM Tris-HCl, 5 mM CaCl2, 150 mM NaCl, and 0.02% (w/v) NaN3, pH 7.6, supplemented with 10 mM L-cysteine, at 37°C
-
0.0000053
prodomain of arginine-specific gingipain B
-
isoform HRgpA, in 200 mM Tris-HCl, 5 mM CaCl2, 150 mM NaCl, and 0.02% (w/v) NaN3, pH 7.6, supplemented with 10 mM L-cysteine, at 37°C
-
0.0000062
prodomain of arginine-specific gingipain B
-
isoform RgpB, in 200 mM Tris-HCl, 5 mM CaCl2, 150 mM NaCl, and 0.02% (w/v) NaN3, pH 7.6, supplemented with 10 mM L-cysteine, at 37°C
-
additional information
additional information
-
inhibition kinetics
-
additional information
additional information
-
Ki-values for benzamidine derivatives in presence or absence of Zn2+
-
additional information
additional information
-
inhibition kinetics, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000071
prodomain of arginine-specific gingipain B
Porphyromonas gingivalis
-
isoform RgpB, with azocoll as substrate, in 200 mM Tris-HCl, 5 mM CaCl2, 150 mM NaCl, and 0.02% (w/v) NaN3, pH 7.6, supplemented with 10 mM L-cysteine, at 37°C
-
0.0000072
prodomain of arginine-specific gingipain B
Porphyromonas gingivalis
-
isoform RgpB, with H-Arg-7-amido-4-methylcoumarin as substrate, in 200 mM Tris-HCl, 5 mM CaCl2, 150 mM NaCl, and 0.02% (w/v) NaN3, pH 7.6, supplemented with 10 mM L-cysteine, at 37°C
-
0.0000237
prodomain of arginine-specific gingipain B
Porphyromonas gingivalis
-
isoform RgpB, with Nalpha-benzoyl-L-arginine 4-nitroanilide as substrate, in 200 mM Tris-HCl, 5 mM CaCl2, 150 mM NaCl, and 0.02% (w/v) NaN3, pH 7.6, supplemented with 10 mM L-cysteine, at 37°C
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
quantification of hepatocyte growth factor induction by RgpB and HRgpA
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
9.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 9.5
5 - 9.5
50% activity at pH 5.0, maximal activity at pH 9.5
5 - 9.5
-
isoform RgpB has a broad pH optimum in the range of pH 9.5 (100% activity) down to pH 5.0 (50%)
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
37
37
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 37
-
with denatured substrate collagen type I, native collagen type I is only degraded at 37°C
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.1
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
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
-
Porphyromonas gingivalis secretes outer membrane vesicles that contain major virulence factors, including Arg-gingipain and Lys-gingipain
additional information
-
in extracellular vesicles and soluble in the culture supernatant
-
additional information
-
localization pattern in strain FLL203 is affected upon cell growth at 42°C
-
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
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
additional information
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
malfunction
-
Porphyromonas gingivalis double mutant RgpA/RgpB cells do not induce apoptosis in human gingvial epithelial cells
malfunction
-
Porphyromonas gingivalis RgpA/B double mutant do not induce buccal edema and gingivitis in BALB/c or C57BL/6 mice
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
-
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
metabolism
-
methaemoglobin formation by R-gingipain facilitates extraction of haem from haemoglobin by HmuY (haem-binding protein)
metabolism
-
the presence of Rgps promotes caspase-1 activation. The caspase-1-dependent interleukin-1beta response is cooperatively diminished by isoforms RgpA and RgpB
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
-
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
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) mediate strong upregulation of the expression of pro-inflammatory cytokines (interleukin-1beta and colony stimulatory factor) in macrophages
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
-
gingipains induce the degradation and inactivation of endothelial thrombomodulin which may promote vascular coagulation and inflammation
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
-
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
-
Rgp-cleavage of protease-activated receptor-1 up-regulates expression of cytokines
physiological function
-
results suggest that gingipains may have a role in the resistance of Porphyromonas gingivalis ATCC 49417 to human beta-defensin 3
physiological function
-
Arg-gingipain promotes the aggregation of Treponema denticola in multi-species biofilms
physiological function
isoform RgbB is an odontopathogenic virulence factor
physiological function
-
the activity of the gingipains on the inflammatory and immune response of human gingival fibroblasts are crucial in periodontitis
physiological function
-
the enzyme plays a significant role in induction and regulation of CXCL8 in THP-1 cells
physiological function
-
the isoforms RgpA and RgbB play a critical role in Akt dephosphorylation and inhibit the PI3K/Akt signaling pathway
physiological function
-
major virulence factors in Porphyromas gingivalis
additional information
-
the maturation pathways for RgpA and RgpB are different, the late onset gingipains activity in the vimA-defective mutant is due to activation/maturation of RgpB. The activation of RgpB can involve autolytic processing
additional information
the maturation pathways for RgpA and RgpB are different, the late onset gingipains activity in the vimA-defective mutant is due to activation/maturation of RgpB. The activation of RgpB can involve autolytic processing
additional information
-
the maturation pathways for RgpA and RgpB are different. RgpA activity can be activated in the absence of RgpB. RgpA is VimA-dependent
additional information
the maturation pathways for RgpA and RgpB are different. RgpA activity can be activated in the absence of RgpB. RgpA is VimA-dependent
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45000
48000
48120 - 48150
50000
56000
-
x * 56000, RgpB, calculated from the deduced amino acid sequence
95000
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
48120 - 48150
mature, C-terminally truncated isozymes, amino acid sequence calculation and mass spectroscopy
48120 - 48150
mature, C-terminally truncated isozymes, amino acid sequence calculation, gel filtration and mass spectroscopy
95000
a complex of catalytic and hemagglutinin/adhesin domains, gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
monomer
additional information
?
-
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
monomer
1 * 48019-48369, gingipain R2 isozymes I-IV and laser mass spectroscopy
monomer
1 * 48019-48369, gingipain R2 isozymes I-IV, laser mass spectroscopy
additional information
-
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
-
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
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
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
-
Rgp possesses C-terminal a hemagglutinin domain containing the proteins responsible for coaggregation activity of Porphyromonas gingivalis, overview
additional information
-
RgpA and Kgp proteinase polyprotein domain structure, peptide mass fingerprinting and mass spectrometry, overview
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
-
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
-
x * 95000, HRgpA, SDS-PAGE, 50000, RgpB, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
proteolytic modification
glycoprotein
-
monosaccharide composition of RgpA, expression of RgpB is required for correct glycosylation and stability of monomeric RgpA from strain W50
proteolytic modification
the mature enzyme is C-terminally truncated to 433 amino acid residues
proteolytic modification
-
gingipain R performs autoprocessing and activation to mature enzyme, overview
proteolytic modification
-
RgpA and Kgp proteinases are synthesized as a polyprotein and proteolytically processed to individual proteinases and adhesins, C-terminal processing by carboxypeptidase CPG70
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
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 37°C, alkylation of the active site cysteine by addition of inhibitor, crystallization by sitting-drop vapour diffusion method at 20°C, 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
-
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 37°C, 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 21°C, several weeks, X-ray diffraction structure determination at 1.5-2.16 A resolution and analysis, structure modeling
-
sitting drop vapor diffusion method, using 14% (w/v) polyethylene glycol 6000, 0.1 M sodium acetate, pH 5.0, 0.2 M calcium chloride as reservoir solution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
DELTA435-507
-
largely inactive, incorrect localization in culture supernatant and periplasm
additional information
additional information
-
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
-
mutant RgpA-deficient isogenic strain W501 and RgpB-deficient isogenic strain D7 show 50% of wild-type strain W50 enzyme activity
additional information
-
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
-
strain W501 is deficient for RgpA, strain E8 for Rgp, and strain D7 for RgpB
additional information
-
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
-
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
-
gingipain-deficient Porphyromonas gingivalis mutants lacking both Arg- and Lys-gingipains are unable to induce interleukin-1beta, interleukin-6, and interleukin-8 degradation
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.8 - 8.3
-
stability of RgpA catalytic domain of wild-type and D7 mutant strain at 30°C in absence or presence of 2-mercaptoethanol or Ca2+, overview
668922
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
-
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
LITERATURE
Ca2+ stabilizes the enzyme, while glycyl-glycine destabilizes the enzyme
Ca2+ stabilizes the isozymes, while glycyl-glycine destabilizes the isozymes
expression of RgpB is required for correct glycosylation and stability of monomeric RgpA from strain W50
-
RgpB is stable and active in buffers containing 6 M urea, 0.1% SDS, 1% Triton X-100, and 1% octyl or decylpyranoside
-
RgpB is stable to denaturing agents, e.g. urea, SDS, Triton X-100, and 1% octyl or decylpyranoside
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, buffer with neutral pH, 1-5 mM CaCl2, indefinitely stable
0°C, on ice, buffer with neutral pH, 1-5 mM CaCl2, stable for months
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
benzamidine-Sepharose column chromatography and Sephadex G-25 gel filtration
acetone sulfate precipitation, arginine-Sepharose column chromatography, and Sephadex G-150 gel filtration
-
arginine-Sepharose column chromatography, Mono Q column chromatography, and gel filtration
-
benzamidine-Sepharose column chromatography and Sephadex G-25 gel filtration
enzyme form Arg-gingivain-75, Arg-gingivain-70 and Arg-gingivain-55
-
glutathione-Sepharose column chromatography and Superdex 75 gel filtration
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
-
native enzymes by ammonium sulfate fractionation, ion exchange and affinity chromatography, RgpA and RgpB by different methods, overview
-
RGP-A and RGP-B, from envelope material, solubilization by detergent 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate, i.e. CHAPS
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
different enzyme fragments expressed as His-tag fusion proteins in Escherichia coli BL21(DE3)
-
expression of wild-type and mutant enzymes in murine ST2 osteoblastic/stromal cells
-
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)
-
RgpB with the C-terminal His-tag is produced by the Porphyromonas gingivalis W83 strain bearing the modified rgpB gene
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
biotechnology
-
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
-
the enzyme activity is used for detection of periodontitis at an early stage of the disease
drug development
-
potential target for the development of an anti-periodontitis vaccination
medicine
molecular biology
-
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
-
enzyme structure is an excellent template for the rational design of drugs with a potential to cure and prevent periodontitis
medicine
-
development of structure-based inhibitors for treatment of periodontal diseases
medicine
-
development of potent, gingipain-specific inhibitors might be a helpful tool in a therapeutic strategy to prevent or treat periodontal disease
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TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kirszbaum, L.; Sotiropoulos, C.; Jackson, C.; Cleal, S.; Slakeski, N.; Reynolds, E.C.
Complete nucleotide sequence of a gene prtR of Porphyromonas gingivalis W50 encoding a 132 kDa protein that contains an arginine-specific thiol endopeptidase domain and a haemagglutinin domain
Biochem. Biophys. Res. Commun.
207
424-431
1995
Porphyromonas gingivalis, Porphyromonas gingivalis W50
Chen, Z.; Potempa, J.; Polanowski, A.; Wikstrom, M.; Travis, J.
Purification and characterization of a 50-kDa cysteine proteinase (gingipain) from Porphyromonas gingivalis
J. Biol. Chem.
267
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1992
Porphyromonas gingivalis
Pavloff, N.; Potempa, J.; Pike, R.N.; Prochazka, V.; Kiefer, M.C.; Travis, J.; Barr, P.J.
Molecular cloning and structural characterization of the Arg-gingipain proteinase of Porphyromonas gingivalis. Biosynthesis as a proteinase-adhesin polyprotein
J. Biol. Chem.
270
1007-1010
1995
Porphyromonas gingivalis
Nakayama, K.; Kadowaki, T.; Okamoto, K.; Yamamoto, K.
Construction and characterization of arginine-specific cysteine proteinase (Arg-gingipain)-deficient mutants of Porphyromonas gingivalis. Evidence for significant contribution of Arg-gingipain to virulence
J. Biol. Chem.
270
23619-23626
1995
Porphyromonas gingivalis
Potempa, J.; Pike, R.; Travis, J.
The multiple forms of trypsin-like activity present in various strains of Porphyromonas gingivalis are due to the presence of either Arg-gingipain or Lys-gingipain
Infect. Immun.
63
1176-1182
1995
Porphyromonas gingivalis, Porphyromonas gingivalis H66
Bedi, G.S.
Purification and characterization of lysine- and arginine-specific gingivain proteases from Porphyromonas gingivalis
Prep. Biochem.
24
251-261
1994
Porphyromonas gingivalis
Fujimura, S.; Hirai, K.; Shibata, Y.; Nakayama, K.; Nakamura, T.
Comparative properties of envelope-associated arginine-gingipains and lysine-gingipain of Porphyromonas gingivalis
FEMS Microbiol. Lett.
163
173-179
1998
Porphyromonas gingivalis
Sroka, A.; Sztukowska, M.; Potempa, J.; Travis, J.; Genco, C.A.
Degradation of host heme proteins by lysine- and arginine-specific cysteine proteinases (gingipains) of Porphyromonas gingivalis
J. Bacteriol.
183
5609-5616
2001
Porphyromonas gingivalis, Porphyromonas gingivalis A7436
Ally, N.; Whisstock, J.C.; Sieprawska-Lupa, M.; Potempa, J.; Le Bonniec, B.F.; Travis, J.; Pike, R.N.
Characterization of the specificity of arginine-specific gingipains from Porphyromonas gingivalis reveals active site differences between different forms of the enzymes
Biochemistry
42
11693-11700
2003
Porphyromonas gingivalis
Banbula, A.; Mak, P.; Smoluch, M.; Travis, J.; Potempa, J.
Arginine-specific cysteine proteinase from Porphyromonas gingivalis as a convenient tool in protein chemistry
Biol. Chem.
382
1399-1404
2001
Porphyromonas gingivalis
Baba, A.; Abe, N.; Kadowaki, T.; Nakanishi, H.; Ohishi, M.; Asao, T.; Yamamoto, K.
Arg-gingipain is responsible for the degradation of cell adhesion molecules of human gingival fibroblasts and their death induced by Porphyromonas gingivalis
Biol. Chem.
382
817-824
2001
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC 33277
Krauser, A.; Potempa, J.; Travis, J.; Powers, J.C.
Inhibition f arginie gingipains (RgpB and HRgpA) with benzamidine inhibitors: zinc increases inhibitory potency
Biol. Chem.
383
1193-1198
2002
Porphyromonas gingivalis
Eichinger, A.; Beisel, H.G.; Jacob, U.; Huber, R.; Medrano, F.J.; Banbula, A.; Potempa, J.; Travis, J.; Bode, W.
Crystal structure of gingipain R: an Arg-specific bacterial cysteine proteinase with caspase-like fold
EMBO J.
18
5453-5462
1999
Porphyromonas gingivalis, Porphyromonas gingivalis HG66
Houle, M.A.; Grenier, D.; Plamodon, P.; Nakayama, K.
The collagenase activity of Porphyromonas gingivalis is due to Arg-gingipain
FEMS Microbiol. Lett.
221
181-185
2003
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC 33277
Potempa, J.; Mikolajczyk-Pawlinska, J.; Brassell, D.; Nelson, D.; Thogersen, I.B.; Enghild, J.J.; Travis, J.
Comparative properties of two cysteine proteinases (gingipains R), the products of two related but individual genes of Porphyromonas gingivalis
J. Biol. Chem.
273
21648-21657
1998
Porphyromonas gingivalis, Porphyromonas gingivalis (B2RKU0), Porphyromonas gingivalis (Q51844), Porphyromonas gingivalis HG66, Porphyromonas gingivalis HG66 (Q51844), Porphyromonas gingivalis ATCC 33277 (B2RKU0)
Imamura, T.; Banbula, A.; Pereira, P.J.B.; TRavis, J.; Potempa, J.
Activation of human prothrombin by arginine-specific cysteine proteinases (gingipain R) from POrphyromonas gingivalis
J. Biol. Chem.
276
18984-18991
2001
Porphyromonas gingivalis
Banbula, A.; Potempa, J.; Travis, J.; Bode, W.; Medrano, F.J.
Crystallization and preliminary X-ray diffraction analysis of gingipain R2 from Porphyromonas gingivalis in complex with H-D-Phe-Phe-Arg-chloromethylketone
Protein Sci.
7
1259-1261
1998
Porphyromonas gingivalis
Smalley, J.W.; Thomas, M.F.; Birss, A.J.; Withnall, R.; Silver, J.
A combination of both arginine- and lysine-specific gingipain activity of Porphyromonas gingivalis is necessary for the generation of the micro-oxo bishaem-containing pigment from haemoglobin
Biochem. J.
379
833-840
2004
Porphyromonas gingivalis
Abe, N.; Baba, A.; Takii, R.; Nakayama, K.; Kamaguchi, A.; Shibata, Y.; Abiko, Y.; Okamoto, K.; Kadowaki, T.; Yamamoto, K.
Roles of Arg- and Lys-gingipains in coaggregation of Porphyromonas gingivalis: identification of its responsible molecules in translation products of rgpA, kgp, and hagA genes
Biol. Chem.
385
1041-1047
2004
Porphyromonas gingivalis
Liu, X.; Sroka, A.; Potempa, J.; Genco, C.A.
Coordinate expression of the Porphyromonas gingivalis lysine-specific gingipain proteinase, Kgp, arginine-specific gingipain proteinase, RgpA, and the heme/hemoglobin receptor, HmuR
Biol. Chem.
385
1049-1057
2004
Porphyromonas gingivalis
Imamura, T.; Potempa, J.; Travis, J.
Gingipain R
Handbook of Proteolytic Enzymes (Barrett, A. J. ; Rawlings, N. D. ; Woessner, J. F. ; eds. )
2
1319-1328
2004
Porphyromonas gingivalis
-
Veith, P.D.; Chen, Y.Y.; Reynolds, E.C.
Porphyromonas gingivalis RgpA and Kgp proteinases and adhesins are C terminally processed by the carboxypeptidase CPG70
Infect. Immun.
72
3655-3657
2004
Porphyromonas gingivalis, Porphyromonas gingivalis RgpA
Mezyk-Kopec, R.; Bzowska, M.; Potempa, J.; Bzowska, M.; Jura, N.; Sroka, A.; Black, R.A.; Bereta, J.
Inactivation of membrane tumor necrosis factor alpha by gingipains from Porphyromonas gingivalis
Infect. Immun.
73
1506-1514
2005
Porphyromonas gingivalis
Rangarajan, M.; Hashim, A.; Aduse-Opoku, J.; Paramonov, N.; Hounsell, E.F.; Curtis, M.A.
Expression of Arg-gingipain RgpB is required for correct glycosylation and stability of monomeric Arg-gingipain RgpA from Porphyromonas gingivalis W50
Infect. Immun.
73
4864-4878
2005
Porphyromonas gingivalis
Uehara, A.; Muramoto, K.; Imamura, T.; Nakayama, K.; Potempa, J.; Travis, J.; Sugawara, S.; Takada, H.
Arginine-specific gingipains from Porphyromonas gingivalis stimulate production of hepatocyte growth factor (scatter factor) through protease-activated receptors in human gingival fibroblasts in culture
J. Immunol.
175
6076-6084
2005
Porphyromonas gingivalis, Porphyromonas gingivalis HG66
Bialas, A.; Grembecka, J.; Krowarsch, D.; Otlewski, J.; Potempa, J.; Mucha, A.
Exploring the Sn binding pockets in gingipains by newly developed inhibitors: structure-based design, chemistry, and activity
J. Med. Chem.
49
1744-1753
2006
Porphyromonas gingivalis, Porphyromonas gingivalis HG66
Kishimoto, M.; Yoshimura, A.; Naito, M.; Okamoto, K.; Yamamoto, K.; Golenbock, D.T.; Hara, Y.; Nakayama, K.
Gingipains inactivate a cell surface ligand on Porphyromonas gingivalis that induces TLR2-and TLR4-independent signaling
Microbiol. Immunol.
50
315-325
2006
Porphyromonas gingivalis
Naito, M.; Sakai, E.; Shi, Y.; Ideguchi, H.; Shoji, M.; Ohara, N.; Yamamoto, K.; Nakayama, K.
Porphyromonas gingivalis-induced platelet aggregation in plasma depends on Hgp44 adhesin but not Rgp proteinase
Mol. Microbiol.
59
152-167
2006
Porphyromonas gingivalis
Cronan, C.A.; Potempa, J.; Travis, J.; Mayo, J.A.
Inhibition of Porphyromonas gingivalis proteinases (gingipains) by chlorhexidine: synergistic effect of Zn(II)
Oral Microbiol. Immunol.
21
212-217
2006
Porphyromonas gingivalis
Smalley, J.W.; Birss, A.J.; Szmigielski, B.; Potempa, J.
Sequential action of R- and K-specific gingipains of Porphyromonas gingivalis in the generation of the haem-containing pigment from oxyhemoglobin
Arch. Biochem. Biophys.
465
44-49
2007
Porphyromonas gingivalis, Porphyromonas gingivalis HG66
Hashimoto, M.; Kadowaki, T.; Tsukuba, T.; Yamamoto, K.
Selective proteolysis of apolipoprotein B-100 by Arg-gingipain mediates atherosclerosis progression accelerated by bacterial exposure
J. Biochem.
140
713-723
2006
Porphyromonas gingivalis
Into, T.; Inomata, M.; Kanno, Y.; Matsuyama, T.; Machigashira, M.; Izumi, Y.; Imamura, T.; Nakashima, M.; Noguchi, T.; Matsushita, K.
Arginine-specific gingipains from Porphyromonas gingivalis deprive protective functions of secretory leucocyte protease inhibitor in periodontal tissue
Clin. Exp. Immunol.
145
545-554
2006
Porphyromonas gingivalis
Yun, L.W.; Decarlo, A.A.; Hunter, N.
Blockade of protease-activated receptors on T cells correlates with altered proteolysis of CD27 by gingipains of Porphyromonas gingivalis
Clin. Exp. Immunol.
150
217-229
2007
Porphyromonas gingivalis
Yasaki-Inagaki, Y.; Inagaki, S.; Yamada, S.; Okuda, K.; Ishihara, K.
Production of protective antibodies against Porphyromonas gingivalis strains by immunization with recombinant gingipain domains
FEMS Immunol. Med. Microbiol.
47
287-295
2006
Porphyromonas gingivalis
Kato, T.; Tsuda, T.; Omori, H.; Kato, T.; Yoshimori, T.; Amano, A.
Maturation of fimbria precursor protein by exogenous gingipains in Porphyromonas gingivalis gingipain-null mutant
FEMS Microbiol. Lett.
273
96-102
2007
Porphyromonas gingivalis
Sheets, S.M.; Potempa, J.; Travis, J.; Fletcher, H.M.; Casiano, C.A.
Gingipains from Porphyromonas gingivalis W83 synergistically disrupt endothelial cell adhesion and can induce caspase-independent apoptosis
Infect. Immun.
74
5667-5678
2006
Porphyromonas gingivalis
Seers, C.A.; Slakeski, N.; Veith, P.D.; Nikolof, T.; Chen, Y.Y.; Dashper, S.G.; Reynolds, E.C.
The RgpB C-terminal domain has a role in attachment of RgpB to the outer membrane and belongs to a novel C-terminal-domain family found in Porphyromonas gingivalis
J. Bacteriol.
188
6376-6386
2006
Porphyromonas gingivalis
Popadiak, K.; Potempa, J.; Riesbeck, K.; Blom, A.M.
Biphasic effect of gingipains from Porphyromonas gingivalis on the human complement system
J. Immunol.
178
7242-7250
2007
Porphyromonas gingivalis
Belibasakis, G.N.; Bostanci, N.; Hashim, A.; Johansson, A.; Aduse-Opoku, J.; Curtis, M.A.; Hughes, F.J.
Regulation of RANKL and OPG gene expression in human gingival fibroblasts and periodontal ligament cells by Porphyromonas gingivalis: a putative role of the Arg-gingipains
Microb. Pathog.
43
46-53
2007
Porphyromonas gingivalis
Saiki, K.; Konishi, K.
Identification of a Porphyromonas gingivalis novel protein sov required for the secretion of gingipains
Microbiol. Immunol.
51
483-491
2007
Porphyromonas gingivalis
Roy, F.; Vanterpool, E.; Fletcher, H.M.
HtrA in Porphyromonas gingivalis can regulate growth and gingipain activity under stressful environmental conditions
Microbiology
152
3391-3398
2006
Porphyromonas gingivalis
Andrian, E.; Grenier, D.; Rouabhia, M.
Porphyromonas gingivalis gingipains mediate the shedding of syndecan-1 from the surface of gingival epithelial cells
Oral Microbiol. Immunol.
21
123-128
2006
Porphyromonas gingivalis
Uehara, A.; Imamura, T.; Potempa, J.; Travis, J.; Takada, H.
Gingipains from Porphyromonas gingivalis synergistically induce the production of proinflammatory cytokines through protease-activated receptors with Toll-like receptor and NOD1/2 ligands in human monocytic cells
Cell. Microbiol.
10
1181-1189
2008
Porphyromonas gingivalis
Boisvert, H.; Duncan, M.J.
Clathrin-dependent entry of a gingipain adhesin peptide and Porphyromonas gingivalis into host cells
Cell. Microbiol.
10
2538-2552
2008
Porphyromonas gingivalis
Uehara, A.; Naito, M.; Imamura, T.; Potempa, J.; Travis, J.; Nakayama, K.; Takada, H.
Dual regulation of interleukin-8 production in human oral epithelial cells upon stimulation with gingipains from Porphyromonas gingivalis
J. Med. Microbiol.
57
500-507
2008
Porphyromonas gingivalis
Bania, J.; Kubiak, A.; Wojtachnio, K.; Polanowski, A.
Pancreatic secretory trypsin inhibitor acts as an effective inhibitor of cysteine proteinases gingipains from Porphyromonas gingivalis
J. Periodont. Res.
43
232-236
2008
Porphyromonas gingivalis
Kato, T.; Tsuda, T.; Inaba, H.; Kawai, S.; Okahashi, N.; Shibata, Y.; Abiko, Y.; Amano, A.
Porphyromonas gingivalis gingipains cause G(1) arrest in osteoblastic/stromal cells
Oral Microbiol. Immunol.
23
158-164
2008
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC 33277
Stathopoulou, P.G.; Benakanakere, M.R.; Galicia, J.C.; Kinane, D.F.
The host cytokine response to Porphyromonas gingivalis is modified by gingipains
Oral Microbiol. Immunol.
24
11-17
2009
Porphyromonas gingivalis
Taiyoji, M.; Shitomi, Y.; Taniguchi, M.; Saitoh, E.; Ohtsubo, S.
Identification of proteinaceous inhibitors of a cysteine proteinase (an Arg-specific gingipain) from Porphyromonas gingivalis in rice grain, using targeted-proteomics approaches
J. Proteome Res.
8
5165-5174
2009
Porphyromonas gingivalis
Kantyka, T.; Latendorf, T.; Wiedow, O.; Bartels, J.; Glaeser, R.; Dubin, G.; Schroeder, J.M.; Potempa, J.; Meyer-Hoffert, U.
Elafin is specifically inactivated by RgpB from Porphyromonas gingivalis by distinct proteolytic cleavage
Biol. Chem.
390
1313-1320
2009
Porphyromonas gingivalis (P28784), Porphyromonas gingivalis (P95493)
Stathopoulou, P.; Galicia, J.; Benakanakere, M.; Garcia, C.; Potempa, J.; Kinane, D.
Porphyromonas gingivalis induce apoptosis in human gingival epithelial cells through a gingipain-dependent mechanism
BMC Microbiol.
9
107
2009
Porphyromonas gingivalis
Kuboniwa, M.; Amano, A.; Hashino, E.; Yamamoto, Y.; Inaba, H.; Hamada, N.; Nakayama, K.; Tribble, G.D.; Lamont, R.J.; Shizukuishi, S.
Distinct roles of long/short fimbriae and gingipains in homotypic biofilm development by Porphyromonas gingivalis
BMC Microbiol.
9
105
2009
Porphyromonas gingivalis
Saiki, K.; Konishi, K.
The role of Sov protein in the secretion of gingipain protease virulence factors of Porphyromonas gingivalis
FEMS Microbiol. Lett.
302
166-174
2010
Porphyromonas gingivalis
Haruyama, K.; Yoshimura, A.; Naito, M.; Kishimoto, M.; Shoji, M.; Abiko, Y.; Hara, Y.; Nakayama, K.
Identification of a gingipain-sensitive surface ligand of Porphyromonas gingivalis that induces Toll-like receptor 2- and 4-independent NF-kappaB activation in CHO cells
Infect. Immun.
77
4414-4420
2009
Porphyromonas gingivalis
Furuta, N.; Takeuchi, H.; Amano, A.
Entry of Porphyromonas gingivalis outer membrane vesicles into epithelial cells causes cellular functional impairment
Infect. Immun.
77
4761-4770
2009
Porphyromonas gingivalis
Monteiro, A.C.; Scovino, A.; Raposo, S.; Gaze, V.M.; Cruz, C.; Svensjoe, E.; Narciso, M.S.; Colombo, A.P.; Pesquero, J.B.; Feres-Filho, E.; Nguyen, K.A.; Sroka, A.; Potempa, J.; Scharfstein, J.
Kinin danger signals proteolytically released by gingipain induce Fimbriae-specific IFN-gamma- and IL-17-producing T cells in mice infected intramucosally with Porphyromonas gingivalis
J. Immunol.
183
3700-3711
2009
Porphyromonas gingivalis
Fitzpatrick, R.E.; Aprico, A.; Wijeyewickrema, L.C.; Pagel, C.N.; Wong, D.M.; Potempa, J.; Mackie, E.J.; Pike, R.N.
High molecular weight gingipains from Porphyromonas gingivalis induce cytokine responses from human macrophage-like cells via a nonproteolytic mechanism
J. Innate Immun.
1
109-117
2009
Porphyromonas gingivalis
Inomata, M.; Ishihara, Y.; Matsuyama, T.; Imamura, T.; Maruyama, I.; Noguchi, T.; Matsushita, K.
Degradation of vascular endothelial thrombomodulin by arginine- and lysine-specific cysteine proteases from Porphyromonas gingivalis
J. Periodontol.
80
1511-1517
2009
Porphyromonas gingivalis
Giacaman, R.A.; Asrani, A.C.; Ross, K.F.; Herzberg, M.C.
Cleavage of protease-activated receptors on an immortalized oral epithelial cell line by Porphyromonas gingivalis gingipains
Microbiology
155
3238-3246
2009
Porphyromonas gingivalis
Li, N.; Yun, P.; Nadkarni, M.; Ghadikolaee, N.; Nguyen, K.; Lee, M.; Hunter, N.; Collyer, C.
Structure determination and analysis of a haemolytic gingipain adhesin domain from Porphyromonas gingivalis
Mol. Microbiol.
76
861-873
2010
Porphyromonas gingivalis
Skottrup, P.D.; Leonard, P.; Kaczmarek, J.Z.; Veillard, F.; Enghild, J.J.; OKennedy, R.; Sroka, A.; Clausen, R.P.; Potempa, J.; Riise, E.
Diagnostic evaluation of a nanobody with picomolar affinity toward the protease RgpB from Porphyromonas gingivalis
Anal. Biochem.
415
158-167
2011
Porphyromonas gingivalis
Toh, E.C.; Dashper, S.G.; Huq, N.L.; Attard, T.J.; OBrien-Simpson, N.M.; Chen, Y.Y.; Cross, K.J.; Stanton, D.P.; Paolini, R.A.; Reynolds, E.C.
Porphyromonas gingivalis cysteine proteinase inhibition by kappa-casein peptides
Antimicrob. Agents Chemother.
55
1155-1161
2011
Porphyromonas gingivalis
Dashper, S.G.; Pan, Y.; Veith, P.D.; Chen, Y.Y.; Toh, E.C.; Liu, S.W.; Cross, K.J.; Reynolds, E.C.
Lactoferrin inhibits Porphyromonas gingivalis proteinases and has sustained biofilm inhibitory activity
Antimicrob. Agents Chemother.
56
1548-1556
2012
Porphyromonas gingivalis
Maisetta, G.; Brancatisano, F.; Esin, S.; Campa, M.; Batoni, G.
Gingipains produced by Porphyromonas gingivalis ATCC49417 degrade human-beta-defensin 3 and affect peptides antibacterial activity in vitro
Peptides
32
1073-1077
2011
Porphyromonas gingivalis
Smalley, J.; Byrne, D.; Birss, A.; Wojtowicz, H.; Sroka, A.; Potempa, J.; Olczak, T.
HmuY haemophore and gingipain proteases constitute a unique syntrophic system of haem acquisition by Porphyromonas gingivalis
PLoS ONE
6
e17182
2011
Porphyromonas gingivalis
Veillard, F.; Sztukowska, M.; Mizgalska, D.; Ksiazek, M.; Houston, J.; Potempa, B.; Enghild, J.J.; Thogersen, I.B.; Gomis-Rueth, F.X.; Nguyen, K.A.; Potempa, J.
Inhibition of gingipains by their profragments as the mechanism protecting Porphyromonas gingivalis against premature activation of secreted proteases
Biochim. Biophys. Acta
1830
4218-4228
2013
Porphyromonas gingivalis, Porphyromonas gingivalis HG66
Ruggiero, S.; Cosgarea, R.; Potempa, J.; Potempa, B.; Eick, S.; Chiquet, M.
Cleavage of extracellular matrix in periodontitis: gingipains differentially affect cell adhesion activities of fibronectin and tenascin-C
Biochim. Biophys. Acta
1832
517-526
2013
Porphyromonas gingivalis
Veillard, F.; Potempa, B.; Guo, Y.; Ksiazek, M.; Sztukowska, M.N.; Houston, J.A.; Koneru, L.; Nguyen, K.A.; Potempa, J.
Purification and characterisation of recombinant His-tagged RgpB gingipain from Porphymonas gingivalis
Biol. Chem.
396
377-384
2015
Porphyromonas gingivalis
Taniguchi, M.; Matsuhashi, Y.; Abe, T.K.; Ishiyama, Y.; Saitoh, E.; Kato, T.; Ochiai, A.; Tanaka, T.
Contribution of cationic amino acids toward the inhibition of Arg-specific cysteine proteinase (Arg-gingipain) by the antimicrobial dodecapeptide, CL(14-25), from rice protein
Biopolymers
102
379-389
2014
Porphyromonas gingivalis (B2RKK0), Porphyromonas gingivalis, Porphyromonas gingivalis ATCC 33277 (B2RKK0)
Taiyoji, M.; Yamanaka, T.; Tsuno, T.; Ohtsubo, S.
Potential value of a rice protein extract, containing proteinaceous inhibitors against cysteine proteinases from Porphyromonas gingivalis, for managing periodontal diseases
Biosci. Biotechnol. Biochem.
77
80-86
2013
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC 33277
Jayaprakash, K.; Khalaf, H.; Bengtsson, T.
Gingipains from Porphyromonas gingivalis play a significant role in induction and regulation of CXCL8 in THP-1 cells
BMC Microbiol.
14
193
2014
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC 33277
Bao, K.; Belibasakis, G.N.; Thurnheer, T.; Aduse-Opoku, J.; Curtis, M.A.; Bostanci, N.
Role of Porphyromonas gingivalis gingipains in multi-species biofilm formation
BMC Microbiol.
14
258
2014
Porphyromonas gingivalis, Porphyromonas gingivalis K1A
Jung, Y.J.; Jun, H.K.; Choi, B.K.
Contradictory roles of Porphyromonas gingivalis gingipains in caspase-1 activation
Cell. Microbiol.
17
1304-1319
2015
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC 33277
Kataoka, S.; Baba, A.; Suda, Y.; Takii, R.; Hashimoto, M.; Kawakubo, T.; Asao, T.; Kadowaki, T.; Yamamoto, K.
A novel, potent dual inhibitor of Arg-gingipains and Lys-gingipain as a promising agent for periodontal disease therapy
FASEB J.
28
3564-3578
2014
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC 33277
Chen, Y.Y.; Seers, C.A.; Slakeski, N.; Moore, C.; Zhang, L.; Reynolds, E.C.
Reversible redox regulation of specificity of Arg-gingipain B in Porphyromonas gingivalis
FEBS Lett.
587
1275-1280
2013
Porphyromonas gingivalis, Porphyromonas gingivalis HG66
de Diego, I.; Veillard, F.T.; Guevara, T.; Potempa, B.; Sztukowska, M.; Potempa, J.; Gomis-Rueth, F.X.
Porphyromonas gingivalis virulence factor gingipain RgpB shows a unique zymogenic mechanism for cysteine peptidases
J. Biol. Chem.
288
14287-14296
2013
Porphyromonas gingivalis (P95493), Porphyromonas gingivalis, Porphyromonas gingivalis W83 (P95493)
van der Post, S.; Subramani, D.B.; Baeckstroem, M.; Johansson, M.E.; Vester-Christensen, M.B.; Mandel, U.; Bennett, E.P.; Clausen, H.; Dahlen, G.; Sroka, A.; Potempa, J.; Hansson, G.C.
Site-specific O-glycosylation on the MUC2 mucin protein inhibits cleavage by the Porphyromonas gingivalis secreted cysteine protease (RgpB)
J. Biol. Chem.
288
14636-14646
2013
Porphyromonas gingivalis, Porphyromonas gingivalis HG66
Nakayama, M.; Inoue, T.; Naito, M.; Nakayama, K.; Ohara, N.
Attenuation of the phosphatidylinositol 3-kinase/Akt signaling pathway by Porphyromonas gingivalis gingipains RgpA, RgpB, and Kgp
J. Biol. Chem.
290
5190-5202
2015
Porphyromonas gingivalis
Froehlich, E.; Kantyka, T.; Plaza, K.; Schmidt, K.H.; Pfister, W.; Potempa, J.; Eick, S.
Benzamidine derivatives inhibit the virulence of Porphyromonas gingivalis
Mol. Oral Microbiol.
28
192-203
2013
Porphyromonas gingivalis (P28784), Porphyromonas gingivalis (P95493), Porphyromonas gingivalis, Porphyromonas gingivalis W83 (P95493), Porphyromonas gingivalis ATCC 33277 (P28784)
Haraguchi, A.; Miura, M.; Fujise, O.; Hamachi, T.; Nishimura, F.
Porphyromonas gingivalis gingipain is involved in the detachment and aggregation of Aggregatibacter actinomycetemcomitans biofilm
Mol. Oral Microbiol.
29
131-143
2014
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC 33277
Palm, E.; Khalaf, H.; Bengtsson, T.
Suppression of inflammatory responses of human gingival fibroblasts by gingipains from Porphyromonas gingivalis
Mol. Oral Microbiol.
30
74-85
2015
Porphyromonas gingivalis, Porphyromonas gingivalis ATCC 33277
Cherian, C.; Jannet Vennila, J.; Sharan, L.
Marine bromophenols as an effective inhibitor of virulent proteins (peptidyl arginine deiminase, gingipain R and hemagglutinin A) in Porphyromas gingivalis
Arch. Oral Biol.
100
119-128
2019
Porphyromonas gingivalis
Dou, Y.; Robles, A.; Roy, F.; Aruni, A.; Sandberg, L.; Nothnagel, E.; Fletcher, H.
The roles of RgpB and Kgp in late onset gingipain activity in the vimA-defective mutant of Porphyromonas gingivalis W83
Mol. Oral Microbiol.
30
347-360
2015
Porphyromonas gingivalis, Porphyromonas gingivalis (P95493), Porphyromonas gingivalis W83, Porphyromonas gingivalis W83 (P95493)
Pourhajibagher, M.; Bahador, A.
In silico identification of a therapeutic target for photo-activated disinfection with indocyanine green Modeling and virtual screening analysis of Arg-gingipain from Porphyromonas gingivalis
Photodiagnosis Photodyn. Ther.
18
149-154
2017
Porphyromonas gingivalis (P72197), Porphyromonas gingivalis
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