{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T21:21:28Z","timestamp":1787260888135,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,30]],"date-time":"2019-01-30T00:00:00Z","timestamp":1548806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 la Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["201815"],"award-info":[{"award-number":["201815"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001870","name":"Fundacja na rzecz Nauki Polskiej","doi-asserted-by":"publisher","award":["UMO\u20102015\/19\/N\/NZ1\/00322"],"award-info":[{"award-number":["UMO\u20102015\/19\/N\/NZ1\/00322"]}],"id":[{"id":"10.13039\/501100001870","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001870","name":"Fundacja na rzecz Nauki Polskiej","doi-asserted-by":"publisher","award":["UMO\u20102018\/29\/N\/NZ1\/00992"],"award-info":[{"award-number":["UMO\u20102018\/29\/N\/NZ1\/00992"]}],"id":[{"id":"10.13039\/501100001870","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 DE022597"],"award-info":[{"award-number":["R01 DE022597"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Citrullination is an essential post\u2010translational modification in which the guanidinium group of protein and peptide arginines is deiminated by peptidylarginine deiminases (PADs). When deregulated, excessive citrullination leads to inflammation as in severe periodontal disease (PD) and rheumatoid arthritis (RA). <jats:italic>Porphyromonas gingivalis<\/jats:italic> is the major periodontopathogenic causative agent of PD and also an etiological agent of RA. It secretes a PAD, termed <jats:italic>Porphyromonas<\/jats:italic> PAD (PPAD), which is a virulence factor that causes aberrant citrullination. Analysis of <jats:italic>P. gingivalis<\/jats:italic> genomes of laboratory strains and clinical isolates unveiled a PPAD variant (PPAD\u2010T2), which showed three amino\u2010acid substitutions directly preceding catalytic Residue H<jats:sup>236<\/jats:sup> (G<jats:sup>231<\/jats:sup>N\/E<jats:sup>232<\/jats:sup>T\/N<jats:sup>235<\/jats:sup>D) when compared with PPAD from the reference strain (PPAD\u2010T1). Mutation of these positions in the reference strain resulted in twofold higher cell\u2010associated citrullinating activity. Similar to PPAD\u2010T1, recombinant PPAD\u2010T2 citrullinated arginines at the C\u2010termini of general peptidic substrates but not within peptides. Catalytically, PPAD\u2010T2 showed weaker substrate binding but higher turnover rates than PPAD\u2010T1. In contrast, no differences were found in thermal stability. The 1.6 \u00c5\u2010resolution X\u2010ray crystal structure of PPAD\u2010T2 in complex with the general human PAD inhibitor, Cl\u2010amidine, revealed that the inhibitor moiety is tightly bound and that mutations localize to a loop engaged in substrate\/inhibitor binding. In particular, mutation G<jats:sup>231<\/jats:sup>N caused a slight structural rearrangement, which probably originated the higher substrate turnover observed. The present data compare two natural PPAD variants and will set the pace for the design of specific inhibitors against <jats:italic>P. gingivalis<\/jats:italic>\u2010caused PD.<\/jats:p>","DOI":"10.1002\/pro.3571","type":"journal-article","created":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T10:05:21Z","timestamp":1547460321000},"page":"478-486","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Structure, function, and inhibition of a genomic\/clinical variant of <i>Porphyromonas gingivalis<\/i> peptidylarginine deiminase"],"prefix":"10.1002","volume":"28","author":[{"given":"Grzegorz","family":"Bereta","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology Jagiellonian University  Gronostajowa 7, PL\u201030\u2010387 Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodoros","family":"Goulas","sequence":"additional","affiliation":[{"name":"Proteolysis Laboratory, Structural Biology Unit Molecular Biology Institute of Barcelona, CSIC  Barcelona Science Park, Helix Building, c\/Baldiri Reixac, 15\u201021, E\u201008028 Barcelona, Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Madej","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology Jagiellonian University  Gronostajowa 7, PL\u201030\u2010387 Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Bielecka","sequence":"additional","affiliation":[{"name":"Malopolska Centre of Biotechnology Jagiellonian University  Gronostajowa 7A, PL\u201030\u2010387, Krak\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Sol\u00e0","sequence":"additional","affiliation":[{"name":"Structural MitoLab, Structural Biology Unit Molecular Biology Institute of Barcelona, CSIC  Barcelona Science Park, Helix Building, c\/Baldiri Reixac, 15\u201021, E\u201008028, Barcelona, Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Potempa","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology Jagiellonian University  Gronostajowa 7, PL\u201030\u2010387 Krak\u00f3w Poland"},{"name":"Department of Oral Immunology and Infectious Diseases University of Louisville School of Dentistry  Louisville Kentucky 40202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Xavier Gomis\u2010R\u00fcth","sequence":"additional","affiliation":[{"name":"Proteolysis Laboratory, Structural Biology Unit Molecular Biology Institute of Barcelona, CSIC  Barcelona Science Park, Helix Building, c\/Baldiri Reixac, 15\u201021, E\u201008028 Barcelona, Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,30]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514552491"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.28"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2873"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2017.132"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.5b00003"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.RA118.000696"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38348"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2012.01885.x"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.7.3248-3256.1999"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003627"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep13936"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep11969"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202726"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-207656"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2006.10.014"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2017.1421827"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi061180d"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2014-0304"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C114.617142"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm2008985"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb500933j"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780471729259.mc13c02s05"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(80)90404-2"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1107\/S160057751400825X"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909047337"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889807021206"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.91"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444912001308"},{"key":"e_1_2_5_31_1","first-page":"368","article-title":"Exploiting structure similarity in refinement: automated NCS and target\u2010structure restraints in BUSTER","volume":"68","author":"Smart OS","year":"2012","journal-title":"Acta Cryst"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"}],"container-title":["Protein Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpro.3571","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.3571","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T11:51:24Z","timestamp":1694692284000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pro.3571"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,30]]},"references-count":31,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1002\/pro.3571"],"URL":"https:\/\/doi.org\/10.1002\/pro.3571","archive":["Portico"],"relation":{},"ISSN":["0961-8368","1469-896X"],"issn-type":[{"value":"0961-8368","type":"print"},{"value":"1469-896X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,30]]},"assertion":[{"value":"2018-12-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}