Any feedback?
Information on EC 3.5.3.15 - protein-arginine deiminase and Organism(s) Porphyromonas gingivalis and UniProt Accession Q9RQJ2
for references in articles please use BRENDA:EC3.5.3.15Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
3.5.3.15 protein-arginine deiminaseIUBMB Comments
Also acts on N-acyl-L-arginine and, more slowly, on L-arginine esters.
Specify your search results
Word Map
- 3.5.3.15
-
citrullination
-
rheumatoid
- arthritis
- histone
- autoimmune
-
deimination
- autoantibody
-
anti-citrullinated
- chromatin
-
acpas
- epitope
- synovial
-
padis
- porphyromonas
-
anti-ccp
-
netosis
- periodontitis
- gingivalis
- sclerosis
- fibrinogen
-
anti-cyclic
- vimentin
-
hla-drb1
- elastase
- autoantigens
- ptpn22
-
decondensation
- cl-amidine
-
lupus
- erythematosus
- myeloperoxidase
- pharmacology
-
self-antigens
-
ra-associated
-
gingipains
- synoviocytes
-
rheumatology
- medicine
-
arginyl
-
erosive
- analysis
- drug development
- fibrin
-
non-hla
- filaggrin
The taxonomic range for the selected organisms is: Porphyromonas gingivalis
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
padi4, peptidylarginine deiminase, padi2, peptidyl arginine deiminase, peptidylarginine deiminase 4, padi3, pad-4, padi1, peptidylarginine deiminase type 4, protein arginine deiminase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
deiminase, protein (arginine)
-
-
-
-
HL-60 PAD
-
-
-
-
PAD
PAD-H19
-
-
-
-
PAD-R11
-
-
-
-
PAD-R4
-
-
-
-
peptidylarginine deiminase
Peptidylarginine deiminase type alpha
-
-
-
-
protein arginine deiminase
-
-
-
-
PAD
-
-
-
-
peptidylarginine deiminase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
amidine hydrolysis
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
protein-L-arginine iminohydrolase
Also acts on N-acyl-L-arginine and, more slowly, on L-arginine esters.
CAS REGISTRY NUMBER
COMMENTARY
75536-80-0
-
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
CESSSHHPGIAEFPS-R + H2O
CESSSHHPGIAEFPS-citrulline + NH3
i.e. fibrinogen peptide FibA-R
-
-
?
IHAREIFDSR + H2O
IHAREIFDS-citrulline + NH3
peptide derived from enolase
-
-
?
N-alpha-benzoyl-L-arginine ethyl ester + H2O
N-alpha-benzoyl-L-citrulline ethyl ester + NH3
-
-
-
?
PPGFSPFR + H2O
PPGFSPF-citrulline + NH3
peptide derived from bradykinin
-
-
?
benzoyl-Arg ethyl ester + H2O
benzoyl-citrulline ethyl ester + NH3
-
-
-
-
?
Gly-Gly-L-Arg + H2O
Gly-Gly-L-Cit + NH3
-
88% activity compared to Nalpha-benzoyl-L-arginine ethyl ester
-
-
?
Gly-L-Arg + H2O
Gly-L-Cit + NH3
-
130% activity compared to Nalpha-benzoyl-L-arginine ethyl ester
-
-
?
human vimentin L-arginine + H2O
human vimentin L-citrulline + NH3
-
-
-
-
?
IHAREIFDSR + H2O
IHAREIFDS-citrulline + NH3
peptide derived from enolase
-
-
?
L-Arg-Gly + H2O
L-Cit-Gly + NH3
-
75% activity compared to Nalpha-benzoyl-L-arginine ethyl ester
-
-
?
L-Arg-Gly-Gly + H2O
L-Cit-Gly-Gly + NH3
-
66% activity compared to Nalpha-benzoyl-L-arginine ethyl ester
-
-
?
L-arginine + H2O
L-citrulline + NH3
-
28% activity compared to Nalpha-benzoyl-L-arginine ethyl ester
-
-
?
L-canavanine + H2O
? + NH3
-
0.3% activity compared to L-arginine
-
-
?
L-homoarginine + H2O
? + NH3
-
0.3% activity compared to L-arginine
-
-
?
L-Leu-Trp-Met-Arg + H2O
L-Leu-Trp-Met-Cit + NH3
-
45% activity compared to Nalpha-benzoyl-L-arginine ethyl ester
-
-
?
L-Met-Arg-Phe + H2O
L-Met-Cit-Phe + NH3
-
the substrate shows fastest rate of citrullination with 158% activity compared to Nalpha-benzoyl-L-arginine ethyl ester
-
-
?
L-octopine + H2O
? + NH3
-
16.7% activity compared to L-arginine
-
-
?
N-alpha-benzoyl-L-arginine + H2O
N-alpha-benzoyl-L-citrulline + NH3
-
-
-
-
?
Nalpha-benzoyl-L-arginine ethyl ester + H2O
Nalpha-benzoyl-L-citrulline ethyl ester + NH3
-
100% activity
-
-
?
PPGFSPFR + H2O
PPGFSPF-citrulline + NH3
peptide derived from bradykinin
-
-
?
protein L-Arg + H2O
?
-
peptidylarginine deiminase, acting in concert with arginine-specific proteinases from Porphyromonas gingivalis, promotes the growth of the pathogen in the periodontal pocket, initially by enhancing its survivability and then by assisting the organism in its circumvention of host humoral defenses
-
-
?
yeast enolase L-arginine + H2O
yeast enolase L-citrulline + NH3
-
-
-
-
?
protein L-Arg + H2O
protein L-citrulline + NH3
-
PAD catalyzes the deimination of the guanidino group from peptidylarginine residues of various peptides to produce peptidylcitrulline and ammonia
-
-
?
additional information
?
-
no substrate: peptide GFSPFRSS
-
-
?
additional information
?
-
no substrates: peptides Arg-Gly-Glu, Met-Arg-Phe, fibrinogen peptide CESSSHHPGIAEFPS-R-GK
-
-
?
additional information
?
-
-
no substrates: peptides Arg-Gly-Glu, Met-Arg-Phe, fibrinogen peptide CESSSHHPGIAEFPS-R-GK
-
-
?
additional information
?
-
-
the enzyme undergoes automodification
-
-
?
additional information
?
-
no substrate: peptide GFSPFRSS
-
-
?
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
protein L-Arg + H2O
?
-
peptidylarginine deiminase, acting in concert with arginine-specific proteinases from Porphyromonas gingivalis, promotes the growth of the pathogen in the periodontal pocket, initially by enhancing its survivability and then by assisting the organism in its circumvention of host humoral defenses
-
-
?
protein L-Arg + H2O
protein L-citrulline + NH3
-
PAD catalyzes the deimination of the guanidino group from peptidylarginine residues of various peptides to produce peptidylcitrulline and ammonia
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Cl-amidine
inhibitor binds covalently to the catalytic C351-Sgamma atom, mimicking a reaction intermediate
iodoacetamide
-
PAD exhibits pseudo first-order loss of activity in the presence of 0.1-10 mM iodoacetamide. When substrate (0.8 mM N-alpha-benzoyl-L-arginine) is present in the inactivation reaction, PAD retains 88% activity after a 4 min incubation, compared to only 32% residual activity under the same reaction conditions in the absence of substrate
iodoacetate
-
PAD exhibits pseudo first-order loss of activity in the presence of 0.5-20 mM iodoacetate
additional information
-
substrate protects the enzyme from inactivation
-
additional information
-
1 mM tosyl phenylalanyl chloromethyl ketone and 0.043 mM leupeptin do not inhibit enzyme activity
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 11
-
pH 7.0: about 45% of maximal activity, pH 11.0: about 40% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
90% of enzyme activity is cell surface associated
-
90% of the deiminase activity is cell- or membrane vesicle-associated
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
-
enzyme's presence in inflamed tissue may promote autoimmune reactions by creation of altered host epitopes
physiological function
during catalysis, enzyme undergoes the transformation between protonation state N (both C351 and H236 are neutral) and state I (both residues exist as a thiolate-imidazolium ion pair). State N is calculated to be more stable than state I by 8.46 kcal/mol, and state N can transform to state I via two steps of substrate-assisted proton transfer. Starting from state N, the deamination reaction corresponds to an energy barrier of 18.82 kcal/mol. The deprotonated C351 initiates the nucleophilic attack to the substrate, which is the key step for deamination reaction. Both the deprotonated D238 and H236 can act as the bases to activate the hydrolytic water, which correspond to similar energy barriers ( about 17 kcal/mol)
physiological function
enzyme is important for bacterial adhesion to fungal cells. The level of binding of a Ppad mutant strain is significantly lower than that observed for the wild-type strain. The viability of Porphyromonas gingivalis cells under normoxia increases in the presence of fungal biofilm compared with the bacteria that form single-species biofilm
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
60880
-
calculated mass of truncated PAD with its poly-His and Xpress epitope tags
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
structures of wild-type and mutant C351A, to 1.46 and 1.48 A resolution. Catalysis is mediated by residues Asp130, His236, Asp238, Asn297 and Cys351. Arg152 and Arg154 may determine the substrate specificity
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C351S
-
the mutant is catalytically inactive, exhibiting less than 0.01% wild type activity
additional information
additional information
-
strain T2 shows three amino-acid substitutions directly preceding catalytic residue H236 (G231N/E232T/N235D) when compared with PPAD from the reference strain ATCC 33277. Mutations localize to a loop engaged in substrate/inhibitor binding. Mutation of these positions in the reference strain results in twofold higher cell-associated citrullinating activity. Similar to PPAD-T1, recombinant PPAD-T2 citrullinates arginines at the C-termini of general peptidic substrates but not within peptides
additional information
strain T2 shows three amino-acid substitutions directly preceding catalytic residue H236 (G231N/E232T/N235D) when compared with PPAD from the reference strain ATCC 33277. Mutations localize to a loop engaged in substrate/inhibitor binding. Mutation of these positions in the reference strain results in twofold higher cell-associated citrullinating activity. Similar to PPAD-T1, recombinant PPAD-T2 citrullinates arginines at the C-termini of general peptidic substrates but not within peptides
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
60
-
enzyme activity decreases by 13% following exposure of cells to 60°C for 10 min
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C or -80°C, in presence of the stabilizing factors FMN or FAD, at pH 5.5, 7.5 or 9.0, no appreciable loss of activity
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
in a a triple-culture system of neutrophils and human dental follicle stem cells primed with Porphyromonas gingivalis, infection of dental follicle stem cells with Porphoyromonas gingivalis prolongs the survival of neutrophils and increases their migration. The phenotypic changes depend on direct cellular contacts and PPAD expression by Porphyromonas gingivalis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
McGraw, W.T.; Potempa, J.; Farley, D.; Travis, J.
Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis. Peptidylarginine deiminase
Infect. Immun.
67
3248-3256
1999
Porphyromonas gingivalis
Rodriguez, S.B.; Stitt, B.L.; Ash, D.E.
Cysteine 351 is an essential nucleophile in catalysis by Porphyromonas gingivalis peptidylarginine deiminase
Arch. Biochem. Biophys.
504
190-196
2010
Porphyromonas gingivalis
Abdullah, S.N.; Farmer, E.A.; Spargo, L.; Logan, R.; Gully, N.
Porphyromonas gingivalis peptidylarginine deiminase substrate specificity
Anaerobe
23
102-108
2013
Porphyromonas gingivalis, Porphyromonas gingivalis W50
Montgomery, A.B.; Kopec, J.; Shrestha, L.; Thezenas, M.L.; Burgess-Brown, N.A.; Fischer, R.; Yue, W.W.; Venables, P.J.
Crystal structure of Porphyromonas gingivalis peptidylarginine deiminase implications for autoimmunity in rheumatoid arthritis
Ann. Rheum. Dis.
75
1255-1261
2016
Porphyromonas gingivalis (Q9RQJ2), Porphyromonas gingivalis, Porphyromonas gingivalis W83 (Q9RQJ2)
Kriebel, K.; Hieke, C.; Engelmann, R.; Potempa, J.; Mueller-Hilke, B.; Lang, H.; Kreikemeyer, B.
Porphyromonas gingivalis peptidyl arginine deiminase can modulate neutrophil activity via infection of human dental stem cells
J. Innate Immun.
10
264-278
2018
Porphyromonas gingivalis (Q9RQJ2), Porphyromonas gingivalis, Porphyromonas gingivalis W83 (Q9RQJ2)
Karkowska-Kuleta, J.; Bartnicka, D.; Zawrotniak, M.; Zielinska, G.; Kieronska, A.; Bochenska, O.; Ciaston, I.; Koziel, J.; Potempa, J.; Baster, Z.; Rajfur, Z.; Rapala-Kozik, M.
The activity of bacterial peptidylarginine deiminase is important during formation of dual-species biofilm by periodontal pathogen Porphyromonas gingivalis and opportunistic fungus Candida albicans
Pathog. Dis.
76
fty033
2018
Porphyromonas gingivalis (Q9RQJ2), Porphyromonas gingivalis, Porphyromonas gingivalis W83 (Q9RQJ2)
Bereta, G.; Goulas, T.; Madej, M.; Bielecka, E.; Sola, M.; Potempa, J.; Xavier Gomis-Rueth, F.
Structure, function, and inhibition of a genomic/clinical variant of Porphyromonas gingivalis peptidylarginine deiminase
Protein Sci.
28
478-486
2019
Porphyromonas gingivalis, Porphyromonas gingivalis (Q9RQJ2), Porphyromonas gingivalis ATCC 33277, Porphyromonas gingivalis T2 (Q9RQJ2)
Zhao, C.; Ling, B.; Dong, L.; Liu, Y.
Theoretical insights into the protonation states of active site cysteine and citrullination mechanism of Porphyromonas gingivalis peptidylarginine deiminase
Proteins
85
1518-1528
2017
Porphyromonas gingivalis (Q9RQJ2), Porphyromonas gingivalis, Porphyromonas gingivalis W83 (Q9RQJ2)
EXTERNAL LINKS (specific for EC-Number 3.5.3.15)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
