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Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases

Porphyromonas gingivalis is a major pathogenic bacterium involved in the pathogenesis of periodontitis. Citrullination has been reported as the underlying mechanism of the pathogenesis, which relies on the interplay between two virulence factors of the bacterium, namely gingipain R and the bacterial...

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Autores principales: Chow, Yoke Chan, Yam, Hok Chai, Gunasekaran, Baskaran, Lai, Weng Yeen, Wo, Weng Yue, Agarwal, Tarun, Ong, Yien Yien, Cheong, Siew Lee, Tan, Sheri-Ann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9559808/
https://www.ncbi.nlm.nih.gov/pubmed/36250046
http://dx.doi.org/10.3389/fcimb.2022.987683
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author Chow, Yoke Chan
Yam, Hok Chai
Gunasekaran, Baskaran
Lai, Weng Yeen
Wo, Weng Yue
Agarwal, Tarun
Ong, Yien Yien
Cheong, Siew Lee
Tan, Sheri-Ann
author_facet Chow, Yoke Chan
Yam, Hok Chai
Gunasekaran, Baskaran
Lai, Weng Yeen
Wo, Weng Yue
Agarwal, Tarun
Ong, Yien Yien
Cheong, Siew Lee
Tan, Sheri-Ann
author_sort Chow, Yoke Chan
collection PubMed
description Porphyromonas gingivalis is a major pathogenic bacterium involved in the pathogenesis of periodontitis. Citrullination has been reported as the underlying mechanism of the pathogenesis, which relies on the interplay between two virulence factors of the bacterium, namely gingipain R and the bacterial peptidyl arginine deiminase. Gingipain R cleaves host proteins to expose the C-terminal arginines for peptidyl arginine deiminase to citrullinate and generate citrullinated proteins. Apart from carrying out citrullination in the periodontium, the bacterium is found capable of citrullinating proteins present in the host synovial tissues, atherosclerotic plaques and neurons. Studies have suggested that both virulence factors are the key factors that trigger distal effects mediated by citrullination, leading to the development of some non-communicable diseases, such as rheumatoid arthritis, atherosclerosis, and Alzheimer’s disease. Thus, inhibition of these virulence factors not only can mitigate periodontitis, but also can provide new therapeutic solutions for systematic diseases involving bacterial citrullination. Herein, we described both these proteins in terms of their unique structural conformations and biological relevance to different human diseases. Moreover, investigations of inhibitory actions on the enzymes are also enumerated. New approaches for identifying inhibitors for peptidyl arginine deiminase through drug repurposing and virtual screening are also discussed.
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spelling pubmed-95598082022-10-14 Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases Chow, Yoke Chan Yam, Hok Chai Gunasekaran, Baskaran Lai, Weng Yeen Wo, Weng Yue Agarwal, Tarun Ong, Yien Yien Cheong, Siew Lee Tan, Sheri-Ann Front Cell Infect Microbiol Cellular and Infection Microbiology Porphyromonas gingivalis is a major pathogenic bacterium involved in the pathogenesis of periodontitis. Citrullination has been reported as the underlying mechanism of the pathogenesis, which relies on the interplay between two virulence factors of the bacterium, namely gingipain R and the bacterial peptidyl arginine deiminase. Gingipain R cleaves host proteins to expose the C-terminal arginines for peptidyl arginine deiminase to citrullinate and generate citrullinated proteins. Apart from carrying out citrullination in the periodontium, the bacterium is found capable of citrullinating proteins present in the host synovial tissues, atherosclerotic plaques and neurons. Studies have suggested that both virulence factors are the key factors that trigger distal effects mediated by citrullination, leading to the development of some non-communicable diseases, such as rheumatoid arthritis, atherosclerosis, and Alzheimer’s disease. Thus, inhibition of these virulence factors not only can mitigate periodontitis, but also can provide new therapeutic solutions for systematic diseases involving bacterial citrullination. Herein, we described both these proteins in terms of their unique structural conformations and biological relevance to different human diseases. Moreover, investigations of inhibitory actions on the enzymes are also enumerated. New approaches for identifying inhibitors for peptidyl arginine deiminase through drug repurposing and virtual screening are also discussed. Frontiers Media S.A. 2022-09-29 /pmc/articles/PMC9559808/ /pubmed/36250046 http://dx.doi.org/10.3389/fcimb.2022.987683 Text en Copyright © 2022 Chow, Yam, Gunasekaran, Lai, Wo, Agarwal, Ong, Cheong and Tan https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Chow, Yoke Chan
Yam, Hok Chai
Gunasekaran, Baskaran
Lai, Weng Yeen
Wo, Weng Yue
Agarwal, Tarun
Ong, Yien Yien
Cheong, Siew Lee
Tan, Sheri-Ann
Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases
title Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases
title_full Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases
title_fullStr Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases
title_full_unstemmed Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases
title_short Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases
title_sort implications of porphyromonas gingivalis peptidyl arginine deiminase and gingipain r in human health and diseases
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9559808/
https://www.ncbi.nlm.nih.gov/pubmed/36250046
http://dx.doi.org/10.3389/fcimb.2022.987683
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