ArticleAnnals of the rheumatic diseases2016
Crystal structure of Porphyromonas gingivalis peptidylarginine deiminase: implications for autoimmunity in rheumatoid arthritis.
Article in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 74 citations in OpenAlex.
- Pathogens in rheumatoid arthritis: epidemiological, mechanistic, and clinical insights.Biomarker research · 2026Review
- Peptidylarginine deiminase in Porphyromonas gingivalis-derived outer membrane vesicles exacerbates metabolic dysfunction-associated steatotic liver disease through the NPAS2/CYP4A10 pathway.Journal of nanobiotechnology · 2026Article
- Beyond PAD Inhibition: Emerging Avenues and Natural Products for Targeting Citrullination in Immune Diseases.Biomedicines · 2026Review
- Biological properties and potential pathogenic mechanisms of oral bacterial-derived extracellular vesicles in oral and systemic diseases.Extracellular vesicles and circulating nucleic acids · 2026Review
- Pathogenicity ofFrontiers in cellular and infection microbiology · 2026Article
- Pathogenesis ofFrontiers in cellular and infection microbiology · 2026Review
- Immune checkpoint inhibitor-related arthritis and oral disorders: shared pathophysiology and clinical implications for rheumatology and oral health.Cancer cell international · 2025Review
- The Role of Oral and Gut Microbiota in Bone Health: Insights from Bacterial Extracellular Vesicles.Microorganisms · 2025Review
- Citrullination in health and disease: From physiological function to gene regulation.Genes & diseases · 2025Review
- Polymorphic Variants of Peptidylarginine Deiminase Gene fromInternational journal of molecular sciences · 2025Article
- Periodontopathic bacteria in rheumatoid arthritis pathogenesis: bridging clinical associations to molecular mechanisms.Frontiers in immunology · 2025Review
- Oral Microbiome Dysbiosis and Citrullination in Rheumatoid Arthritis.Advances in experimental medicine and biology · 2025Review
- Potential roles and mechanisms of bacterial peptidylarginine deiminase in dental biofilm mediated byJournal of oral microbiology · 2025Review
- Impact of Protein Citrullination by Periodontal Pathobionts on Oral and Systemic Health: A Systematic Review of Preclinical and Clinical Studies.Journal of clinical medicine · 2024Review
- Article
- Identification of a new genetic variant (G231N, E232T, N235D) of peptidylarginine deiminase fromFrontiers in immunology · 2024Article
- Triterpenes as Potential Drug Candidates for Rheumatoid Arthritis Treatment.Life (Basel, Switzerland) · 2023Review
- Porphyromonas gulae and PPAD antibodies are not related to citrullination in rheumatoid arthritis.Clinical oral investigations · 2023Article
- The Interaction Effect of Anti-RgpA and Anti-PPAD Antibody Titers: An Indicator for Rheumatoid Arthritis Diagnosis.Journal of clinical medicine · 2023Article
- Unmet needs and perspectives in rheumatoid arthritis-associated interstitial lung disease: A critical review.Frontiers in medicine · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPeriodontitis (PD) is a known risk factor for rheumatoid arthritis (RA) and there is increasing evidence that the link between the two diseases is due to citrullination by the unique bacterial peptidylarginine deiminase (PAD) enzyme expressed by periodontal pathogen Pophyromonas gingivalis (PPAD). However, the precise mechanism by which PPAD could generate potentially immunogenic peptides has remained controversial due to lack of information about the structural and catalytic mechanisms of the enzyme.
objectivesBy solving the 3D structure of PPAD we aim to characterise activity and elucidate potential mechanisms involved in breach of tolerance to citrullinated proteins in RA.
methodsPPAD and a catalytically inactive mutant PPAD(C351A) were crystallised and their 3D structures solved. Key residues identified from 3D structures were examined by mutations. Fibrinogen and α-enolase were incubated with PPAD and P. gingivalis arginine gingipain (RgpB) and citrullinated peptides formed were sequenced and quantified by mass spectrometry.
resultsHere, we solve the crystal structure of a truncated, highly active form of PPAD. We confirm catalysis is mediated by the following residues: Asp130, His236, Asp238, Asn297 and Cys351 and show Arg152 and Arg154 may determine the substrate specificity of PPAD for C-terminal arginines. We demonstrate the formation of 37 C-terminally citrullinated peptides from fibrinogen and 11 from α-enolase following incubation with tPPAD and RgpB.
conclusionsPPAD displays an unequivocal specificity for C-terminal arginine residues and readily citrullinates peptides from key RA autoantigens. The formation of these novel citrullinated peptides may be involved in breach of tolerance to citrullinated proteins in RA.
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