{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:25:20Z","timestamp":1791221120090,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2011,6,13]],"date-time":"2011-06-13T00:00:00Z","timestamp":1307923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      The physiological and pathological functions of proteinase 3 (PR3) are not well understood due to its close similarity to human neutrophil elastase (HNE) and the lack of a specific inhibitor. Based on structural analysis of the active sites of PR3 and HNE, we generated mutants derived from the polyvalent inhibitor SerpinB1 (monocyte\/neutrophil elastase inhibitor) that specifically inhibit PR3 and that differ from wt\u2010SerpinB1 by only 3 or 4 residues in the reactive center loop. The rate constant of association between the best SerpinB1 mutant and PR3 is 1.4 \u00d7 10\n                      <jats:sup>7<\/jats:sup>\n                      M\n                      <jats:sup>\u20131<\/jats:sup>\n                      \u00b7s\n                      <jats:sup>\u20131<\/jats:sup>\n                      , which is ~100\u2010fold higher than that observed with wt\u2010SerpinB1 and compares with that of \u03b11\u2010protease inhibitor (\u03b11\u2010PI) toward HNE. SerpinB1(S\/DAR) is cleaved by HNE, but due to differences in rate, inhibition of PR3 by SerpinB1(S\/DAR) is only minimally affected by the presence of HNE even when the latter is in excess. SerpinB1(S\/DAR) inhibits soluble PR3 and also membrane\u2010bound PR3 at the surface of activated neutrophils. Moreover, SerpinB1(S\/DAR) clears induced PR3 from the surface of activated neutrophils. Overall, these specific inhibitors of PR3 will be valuable for defining biological functions of the protease and may prove useful as therapeutics for PR3\u2010related inflammatory diseases, such as Wegener's granulomatosis.\u2014J\u00e9got, G., Derache, C., Castella, S., Lahouassa, H., Pitois, E., Jourdan, M. L., Remold\u2010O'Donnell, E., Kellenberger, C., Gauthier, F., Korkmaz, B. A substrate\u2010based approach to convert SerpinB1 into a specific inhibitor of proteinase 3, the Wegener's granulomatosis autoantigen.\n                      <jats:italic>FASEB J.<\/jats:italic>\n                      25, 3019\u20133031 (2011).\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1096\/fj.10-176552","type":"journal-article","created":{"date-parts":[[2011,6,13]],"date-time":"2011-06-13T21:56:17Z","timestamp":1308002177000},"page":"3019-3031","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A substrate\u2010based approach to convert SerpinB1 into a specific inhibitor of proteinase 3, the Wegener's granulomatosis autoantigen"],"prefix":"10.1096","volume":"25","author":[{"given":"Gwenhael","family":"J\u00e9got","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U\u2010618 Prot\u00e9ases et Vectorisation Pulmonaires Tours France"},{"name":"Universit\u00e9 Francois Rabelais Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrystelle","family":"Derache","sequence":"additional","affiliation":[{"name":"Centre de Biophysique Mol\u00e9culaire Centre National de la Recherche Scientifique (CNRS) Orl\u00e9ans France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Castella","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U\u2010618 Prot\u00e9ases et Vectorisation Pulmonaires Tours France"},{"name":"Universit\u00e9 Francois Rabelais Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hichem","family":"Lahouassa","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U\u2010618 Prot\u00e9ases et Vectorisation Pulmonaires Tours France"},{"name":"Universit\u00e9 Francois Rabelais Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Pitois","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U\u2010618 Prot\u00e9ases et Vectorisation Pulmonaires Tours France"},{"name":"Universit\u00e9 Francois Rabelais Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Lise","family":"Jourdan","sequence":"additional","affiliation":[{"name":"Centre Hospitalier R\u00e9gional Universitaire Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Remold\u2010O'Donnell","sequence":"additional","affiliation":[{"name":"Immune Disease Institute Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Kellenberger","sequence":"additional","affiliation":[{"name":"Architecture et Fonction des Macromol\u00e9cules Biologiques CNRS\u2010Unit\u00e9 Mixte de Recherche (UMR) Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Gauthier","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U\u2010618 Prot\u00e9ases et Vectorisation Pulmonaires Tours France"},{"name":"Universit\u00e9 Francois Rabelais Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brice","family":"Korkmaz","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U\u2010618 Prot\u00e9ases et Vectorisation Pulmonaires Tours France"},{"name":"Universit\u00e9 Francois Rabelais Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,6,13]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.002733"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/jam.2004.17.289"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.03.003"},{"key":"e_1_2_5_5_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.2174\/1874306401004010020","article-title":"Antiproteases as therapeutics to target inflammation in cystic fibrosis","volume":"4","author":"Quinn D. J.","year":"2010","journal-title":"Open Respir. Med. J."},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)91167-S"},{"key":"e_1_2_5_7_1","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1001\/jama.1988.03410090091037","article-title":"Biochemical efficacy and safety of monthly augmentation therapy for alpha 1\u2010antitrypsin deficiency","volume":"260","author":"Hubbard R. C.","year":"1988","journal-title":"JAMA"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2103118"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ta.0000217271.25809.a0"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2007.10.009"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/346520a0"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0355"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2007.11.005"},{"key":"e_1_2_5_14_1","first-page":"1113","article-title":"Ultrastructural localization of proteinase 3, the target antigen of anti\u2010cytoplasmic antibodies circulating in Wegener's granulomatosis","volume":"137","author":"Csernok E.","year":"1990","journal-title":"Am. J. Pathol."},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)01073-N"},{"key":"e_1_2_5_16_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1183\/09031936.00143308","article-title":"c\u2010ANCA\u2010induced neutrophil\u2010mediated lung injury: a model of acute Wegener's granulomatosis","volume":"36","author":"Hattar K.","journal-title":"Eur. Respir. J."},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2007.09.007"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2004-0374OC"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2009.12.057"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v25.i5.10"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)33954-6"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R100016200"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/35038119"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00100a022"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.9.4808"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.2.453"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108879200"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202918200"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.63"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2003-0139OC"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608700200"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20020321"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0134(199611)26:3<288::AID-PROT5>3.0.CO;2-A"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6526"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.26.16268"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2006.05257.x"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.20.11866"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401913200"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903887"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)85615-6"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00431.x"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0113925"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1986.tb04521.x"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1996.0458"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.042903"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210074200"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0604319"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.5.3329"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M901471200"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.11.4115"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.169.3.1071"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)81143-N"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr010170"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.24.6.4147"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119662"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198704233161704"},{"key":"e_1_2_5_57_1","article-title":"SerpinB1 in CF airway fluids: quantity, molecular form and mechanism of elastase inhibition","author":"Cooley J.","year":"2010","journal-title":"Eur. Respir. J."},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000034911.03334.C3"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00364.x"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702876200"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.10-176552","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.10-176552","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.10-176552","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T15:49:30Z","timestamp":1761666570000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.10-176552"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,6,13]]},"references-count":59,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2011,9]]}},"alternative-id":["10.1096\/fj.10-176552"],"URL":"https:\/\/doi.org\/10.1096\/fj.10-176552","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,6,13]]},"assertion":[{"value":"2011-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-06-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}