Cited by 378Oral microbiology and periodontitis researchOral and gingival health researchBacterial biofilms and quorum sensing

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Purification, Characterization, and Sequence Analysis of a Potential Virulence Factor from Porphyromonas gingivalis , Peptidylarginine Deiminase

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McGraw, Walker T., Potempa, Jan, Farley, David, Travis, James·1999·Infection and Immunity

DOI 10.1128/iai.67.7.3248-3256.1999PMC PMC116503

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Abstract

The initiation and progression of adult-onset periodontitis has been associated with infection of the gingival sulcus by Porphyromonas gingivalis . This organism utilizes a multitude of virulence factors to evade host defenses as it establishes itself as one of the predominant pathogens in periodontal pockets. A feature common to many other oral pathogens is the production of ammonia due to its protective effect during acidic cleansing cycles in the mouth. Additionally, ammonia production by P. gingivalis has been proposed as a virulence factor due to its negative effects on neutrophil function. In this study, we describe the first purification of a peptidylarginine deiminase (PAD) from a prokaryote. PAD exhibits biochemical characteristics and properties that suggest that it may be a virulence agent. PAD deiminates the guanidino group of carboxyl-terminal arginine residues on a variety of peptides, including the vasoregulatory peptide-hormone bradykinin, to yield ammonia and a citrulline residue. The soluble protein has an apparent mass of 46 kDa, while the DNA sequence predicts a full-length protein of 61.7 kDa. PAD is optimally active at 55°C, stable at low pH, and shows the greatest activity above pH 9.0. Interestingly, in the presence of stabilizing factors, PAD is resistant to limited proteolysis and retains significant activity after short-term boiling. We propose that PAD, acting in concert with arginine-specific proteinases from P. 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.

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BackgroundInfluential
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“McGraw et al ., [20] tested various compounds and reported that the serine-and cysteine protease inhibitor leupeptin is able to completely inhibit PPAD at millimolar levels, with other inhibitors such as thiourea, thio-l-citrulline, and the serine and cysteine protease inhibitor TLCK ( N‑…”
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“Since PPAD was first isolated and characterized in 1999 [13], the enzyme has been suspected to contribute to P. gingivalis virulence.”
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“gingivalis, an anaerobic Gram-negative bacterium that is a keystone oral pathogen in periodontitis (27), was detected in 25% of periodontally healthy participants (28).”
Background
Theoretical insights into the protonation states of active site cysteine and citrullination mechanism of Porphyromonas gingivalis peptidylarginine deiminase
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Authors: McGraw, W. T., Potempa, J., Farley, D., & Travis, J.
Affiliations: University of Georgia (US)
Jagiellonian University (PL)
Department of Arthritis Biology, Novartis Pharmaceuticals, Summit, New Jersey 07901,3 and
ORCID: Potempa, Jan
Travis, James
Venue: Infection and Immunity
Publisher: American Society for Microbiology
Published: 1999-07
Volume: 67
Issue: 7
Pages: 3248-3256
ISSN: 0019-9567 (ISSN-L)
1098-5522
DOI: 10.1128/iai.67.7.3248-3256.1999
PMC: PMC116503
OpenAlex: W1943338444
Cited by: 378
References: 47
Citations by year: 2026: 9 · 2025: 13 · 2024: 12 · 2023: 15 · 2022: 19 · 2021: 15 · 2020: 16 · 2019: 30 · 2018: 24 · 2017: 37 · 2016: 26 · 2015: 28 · 2014: 22 · 2013: 27 · 2012: 20
FWCI: 1.60
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Infection and Immunity (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
Health Sciences › Dentistry › Periodontics › Oral and gingival health research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
Keywords: Porphyromonas gingivalis, peptidylarginine deiminase, virulence factors, periodontitis, ammonia synthesis, bradykinin, citrullination, protein purification, protein stability, host defense evasion, periodontal pockets
MeSH terms: Protein-Arginine Deiminases, Protein-Arginine Deiminase Type 4, Amino Acid Sequence, Base Sequence, Enzyme Activation, Humans, Hydrolases, Molecular Sequence Data, Periodontitis, Virulence, Bacteroidaceae Infections, Porphyromonas gingivalis, Sequence Analysis

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Purification, Characterization, and Sequence Analysis of a Potential Virulence Factor from Porphyromonas gingivalis , Peptidylarginine Deiminase

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