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 hide
3.4.22.37
-
RECOMMENDED NAME
GeneOntology No.
gingipain R
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
hydrolysis of proteins and small molecule substrates, with a preference for Arg in P1
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
CAS REGISTRY NUMBER
COMMENTARY hide
159745-71-8
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain A7436, enzyme forms HRgpA and RgpB
-
-
Manually annotated by BRENDA team
H66
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
RgpA
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
alpha chains of haptoglobin + H2O
?
show the reaction diagram
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
apoB-100 protein + H2O
?
show the reaction diagram
-
apoB-100 degradation induces LDL-modification and contributes to the onset of atherosclerosis
-
-
?
AWTPTPTPLSTPSIIRTTGLRPYPSSVLI + H2O
AWTPTPTPLSTPSIIR + TTGLRPYPSSVLI
show the reaction diagram
azocasein + H2O
?
show the reaction diagram
Azocoll + H2O
?
show the reaction diagram
benzoyl-Arg 4-nitroanilide + H2O
benzoyl-Arg + 4-nitroaniline
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-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
CXCL8 + H2O
?
show the reaction diagram
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
-
-
?
denatured type I collagen + H2O
?
show the reaction diagram
elafin + H2O
?
show the reaction diagram
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
-
?
Fibronectin + H2O
?
show the reaction diagram
-
the enzyme isoforms HRgpA and RgpB effectively destroy the cell-binding domain of fibronectin
-
-
?
Gelatin + H2O
?
show the reaction diagram
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
?
show the reaction diagram
-
degradation of host protein substrate
-
-
?
hemopexin + H2O
hemin + ?
show the reaction diagram
histatin 5 + H2O
?
show the reaction diagram
human beta-defensin 3 + H2O
?
show the reaction diagram
-
-
-
-
?
human protease-activated receptor PAR-1 + H2O
?
show the reaction diagram
human protease-activated receptor PAR-2 + H2O
?
show the reaction diagram
Insulin B-chain + H2O
?
show the reaction diagram
-
specific cleavage of Arg-+-
-
-
-
integrin subunit alpha2 + H2O
?
show the reaction diagram
integrin subunit beta1 + H2O
?
show the reaction diagram
integrin subunit beta3 + H2O
?
show the reaction diagram
interferon gamma + H2O
?
show the reaction diagram
interleukin 12 + H2O
?
show the reaction diagram
interleukin-1beta + H2O
?
show the reaction diagram
interleukin-6 + H2O
?
show the reaction diagram
interleukin-8 + H2O
?
show the reaction diagram
Leu-Tyr-Arg-4-nitroanilide + H2O
Leu-Tyr-Arg + 4-nitroaniline
show the reaction diagram
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-+-
-
-
-
MeoSuc-Ala-Ala-Pro-Val-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
?
Muc2 + H2O
?
show the reaction diagram
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
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-nitroanilide
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-nitroaniline
show the reaction diagram
-
-
-
-
?
Nalpha-benzoyl-L-arginine 4-nitroanilide + H2O
Nalpha-benzoyl-L-arginine + 4-nitroaniline
show the reaction diagram
oxyhaemoglobin + H2O
?
show the reaction diagram
-
-
-
-
?
oxyhaemoglobin + H2O
methaemoglobin
show the reaction diagram
oxyhaemoglobin + H2O
methaemoglobin + ?
show the reaction diagram
prefimbrillin + H2O
fimbrilline + ?
show the reaction diagram
-
-
mature form of the protein
-
?
profibronectin + H2O
fibronectin + ?
show the reaction diagram
protease-activated receptor-1 + H2O
?
show the reaction diagram
-
specific substrate for Arg-gingipain
-
-
?
protein + H2O
peptides
show the reaction diagram
protein C + H2O
?
show the reaction diagram
-
activation through limited proteolysis
-
-
?
prothrombin + H2O
?
show the reaction diagram
-
activation through limited proteolysis
-
-
?
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
thrombin + ?
show the reaction diagram
-
HRgpA, involved in fibrinogen clotting
-
?
RgpA-HagA polyprotein + H2O
?
show the reaction diagram
-
processing of the precursor by Rgp
-
-
?
RgpA-Hgp polyprotein + H2O
?
show the reaction diagram
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
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
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
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
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-7-amido-4-methylcoumarin + H2O
Z-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
Z-Arg-Arg-4-nitroanilide + H2O
Z-Arg-Arg + 4-nitroaniline
show the reaction diagram
synthetic fluorogenic substrate
-
?
Z-Phe-Arg-7-amido-4-methylcoumarin + H2O
Z-Phe-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
CXCL8 + H2O
?
show the reaction diagram
elafin + H2O
?
show the reaction diagram
factor IX proenzyme + H2O
?
show the reaction diagram
-
activation through limited proteolysis
-
-
?
factor X proenzyme + H2O
?
show the reaction diagram
-
activation through limited proteolysis
-
-
?
Fibronectin + H2O
?
show the reaction diagram
-
the enzyme isoforms HRgpA and RgpB effectively destroy the cell-binding domain of fibronectin
-
-
?
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
?
show the reaction diagram
-
degradation of host protein substrate
-
-
?
hemopexin + H2O
hemin + ?
show the reaction diagram
histatin 5 + H2O
?
show the reaction diagram
human protease-activated receptor PAR-1 + H2O
?
show the reaction diagram
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
integrin subunit beta1 + H2O
?
show the reaction diagram
integrin subunit beta3 + H2O
?
show the reaction diagram
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
-
-
?
interleukin-8 + H2O
?
show the reaction diagram
-
biological inactivation and degradation
-
-
?
Muc2 + H2O
?
show the reaction diagram
oxyhaemoglobin + H2O
methaemoglobin
show the reaction diagram
prefimbrillin + H2O
fimbrilline + ?
show the reaction diagram
-
-
mature form of the protein
-
?
profibronectin + H2O
fibronectin + ?
show the reaction diagram
protease-activated receptor-1 + H2O
?
show the reaction diagram
-
specific substrate for Arg-gingipain
-
-
?
protein + H2O
peptides
show the reaction diagram
protein C + H2O
?
show the reaction diagram
-
activation through limited proteolysis
-
-
?
prothrombin + H2O
?
show the reaction diagram
-
activation through limited proteolysis
-
-
?
prothrombin + H2O
thrombin + ?
show the reaction diagram
-
HRgpA, involved in fibrinogen clotting
-
?
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
transferrin + H2O
?
show the reaction diagram
-
degradation of host protein substrate
-
-
?
transferrin + H2O
hemin + ?
show the reaction diagram
transferring receptor + H2O
?
show the reaction diagram
-
Rgp is responsible for transferring receptor degradation
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zn2+
-
enhances the inhibtiroy effect of chlorhexidine
additional information
-
enzyme forms are not affected by Mg2+ and Ca2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,6-bis-(4-amidinobenzyl)-cyclohexanone
;
-
alpha2-Macroglobulin
-
-
-
antipain
benzamidine
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
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
E-64
-
reversible inhibitor
E64
-
reversible, competitive inhibition
EGTA
-
completely reversed by addition of excess Ca2+
FA-70C1
-
potent inhibitor
-
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
iodoacetic acid
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
-
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
N-alpha-tosyl-L-lysyl chloromethyl ketone
N-Chlorosuccinimide
-
-
N-ethylmaleimide
Nalpha-p-tosyl-L-lysine chloromethyl ketone
-
TLCK
p-aminobenzamidine
-
-
p-hydroxymercuribenzoate
-
complete inhibition at 0.2 mM, both enzyme forms
Phe-Arg-fluoromethylketone
-
-
-
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
-
-
prodomain of arginine-specific gingipain A
-
-
-
prodomain of arginine-specific gingipain B
-
-
-
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
-
RLMAAKAESRK
competitive inhibitor
-
RRLMAAKAES
mixed-type inhibitor
-
RRLMAAKAESR
mixed-type inhibitor
-
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
-
tetracyclin
-
uncompetitive
tosyl-L-Lys chloromethyl ketone
-
i.e. TLCK
tosyl-L-lysine chloromethyl ketone
-
i.e. TLCK, both enzyme forms
tosyl-L-lysyl-chloromethane hydrochloride
-
-
-
tosyl-L-Phe chloromethyl ketone
-
i.e. TPCK
YPR-chloromethylketone
-
-
-
Z-FFR-chloromethylketone
-
-
-
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
cysteamine
activates, best above 5 mM
cysteine
dithiothreitol
glutathione
activates, best above 5 mM
glycyl-glycine
glycylglycine
-
stimulates depending on the substrate
L-cysteine
Phospholipids
-
activation of prothrombin cleavage in presence of Ca2+ by HRgpA not RgpB, 1.5fold at 0.04 mg/ml
thiol
-
activates
Urea
-
3fold activation at 6 M, probably due to unfolding of the substrate azocasein, which enhances the enzymes sensitivity for proteolytic cleavage
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00026 - 0.0066
prothrombin
0.0044
Z-Phe-Arg-7-amido-4-methylcoumarin
at pH 7.5 and 37C
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.076 - 0.32
prothrombin
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0029
2,6-bis-(4-amidinobenzyl)-cyclohexanone
at pH 7.6 and 37C; at pH 7.6 and 37C
-
0.536
benzamidine
at pH 7.6 and 37C; at pH 7.6 and 37C
0.013 - 0.03
bis-benzamidine with urea linker
0.0015 - 0.0022
E64
-
-
0.00000024
KYT-1
-
at 40C and pH 7.5
0.1
KYT-36
-
Ki above 0.1 mM, at 40C and pH 7.5
0.00004
KYT-41
-
at 40C and pH 7.5
-
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
-
0.107
Pentamidine
at pH 7.6 and 37C; at pH 7.6 and 37C
0.00000085 - 0.0000021
prodomain of arginine-specific gingipain A
0.0000053 - 0.0000062
prodomain of arginine-specific gingipain B
0.0099
RLMAAKAESRK
at pH 7.5 and 37C
-
0.0013
RRLMAAKAES, RRLMAAKAESR
at pH 7.5 and 37C
-
0.00096
RRLMAAKAESRK
at pH 7.5 and 37C
-
additional information
additional information
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000071 - 0.0000237
prodomain of arginine-specific gingipain B
0.248
RLMAAKAESRK
Porphyromonas gingivalis
B2RKK0
at pH 7.5 and 37C
-
0.242
RRLMAAKAESR
Porphyromonas gingivalis
B2RKK0
at pH 7.5 and 37C
-
0.145
RRLMAAKAESRK
Porphyromonas gingivalis
B2RKK0
at pH 7.5 and 37C
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
40.8
purified isozyme IV
41.3
purified isozyme I
42.9
purified isozyme III
45.5
purified isozyme II
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 8
-
both enzyme forms
7.6 - 8.3
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 9.5
8.5
-
rapid decrease of activity above pH 8.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25 - 37
-
with denatured substrate collagen type I, native collagen type I is only degraded at 37C
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3.74
isoelectric focusing
3.8
-
RGP-B, isoelectric focusing
4 - 5
-
isoelectric focusing
4.7 - 4.8
-
RGP-A, isoelectric focusing
4.96
isozyme IV, isoelectric focusing
5.03
isozyme III, isoelectric focusing
5.09
isozyme II, isoelectric focusing
5.21
isozyme I, isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
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
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
PDB
SCOP
CATH
ORGANISM
UNIPROT
Porphyromonas gingivalis (strain ATCC BAA-308 / W83)
Porphyromonas gingivalis (strain ATCC BAA-308 / W83)
Porphyromonas gingivalis (strain ATCC BAA-308 / W83)
Porphyromonas gingivalis (strain ATCC BAA-308 / W83)
Porphyromonas gingivalis (strain ATCC BAA-308 / W83)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
44000
-
Porphyromonas gingivalis, gel filtration
45000
-
Porphyromonas gingivalis
48120 - 48150
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
55000
-
Porphyromonas gingivalis, enzyme form Arg-gingivain-55
70000
-
Porphyromonas gingivalis, enzyme form Arg-gingivain-70
75000
-
Porphyromonas gingivalis, enzyme form Arg-gingivain-75
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
COMMENTARY hide
LITERATURE
monomer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
proteolytic modification
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 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
-
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
-
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
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.8 - 8.3
-
stability of RgpA catalytic domain of wild-type and D7 mutant strain at 30C in absence or presence of 2-mercaptoethanol or Ca2+, overview
668922
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
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
1% SDS slightly decreases enzyme activity
-
Ca2+ stabilizes
-
Ca2+ stabilizes all forms of gingipain R
-
Ca2+ stabilizes the enzyme, while glycyl-glycine destabilizes the enzyme
Ca2+ stabilizes the isozymes, while glycyl-glycine destabilizes the isozymes
enzyme is completely inactivated in 8 M urea
-
expression of RgpB is required for correct glycosylation and stability of monomeric RgpA from strain W50
-
Irreversible loss of activity during lyophilization
-
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
-20C, buffer with neutral pH, 1-5 mM CaCl2, indefinitely stable
-20C, stable for several months
-
0C, on ice, buffer with neutral pH, 1-5 mM CaCl2, stable for months
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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; benzamidine-Sepharose column chromatography and Sephadex G-25 gel filtration
enzyme form Arg-gingivain-75, Arg-gingivain-70 and Arg-gingivain-55
-
from cell culture medium; isozymes I-IV from cell culture medium, 4.5-5fold
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
-
native extracellular enzyme from culture medium
-
native HRgpA and RgpB
-
native HRgpA and RgpB from culture supernatant
-
nickel-chelating affinity column chromatography
-
recombinant protein using His-tag
-
RGP-A and RGP-B, from envelope material, solubilization by detergent 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate, i.e. CHAPS
-
using affinity and ion exchange chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
different enzyme fragments expressed as His-tag fusion proteins in Escherichia coli BL21(DE3)
-
expressed in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Porphyromonas gingivalis strain ERC129
-
expression of wild-type and mutant enzymes in murine ST2 osteoblastic/stromal cells
-
gene rgpA, expression analysis and regulation
-
initial translation products, overview
-
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
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C244A
-
mature enzyme numbering, inactive, correct localization
DELTA435-507
-
largely inactive, incorrect localization in culture supernatant and periplasm
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
pretreatment with a reducing agent required for activity
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
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