{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:35:38Z","timestamp":1785436538387,"version":"3.56.0"},"reference-count":43,"publisher":"International Union of Crystallography (IUCr)","issue":"11","license":[{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/journals.iucr.org\/services\/copyrightpolicy.html"},{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.iucr.org\/services\/copyrightpolicy.html#TDM"}],"content-domain":{"domain":["iucr.org","wiley.com","iucrj.org"],"crossmark-restriction":true},"short-container-title":["Acta Crystallogr F Struct Biol Commun","Acta Crystallogr F","Acta Crystallogr F Struct Biol Cryst Commun","Acta Cryst F","Acta Cryst F Struct Biol Commun","Acta Cryst Sect F","Acta Cryst Sect F Struct Biol Commun","Acta Crystallogr Sect F","Acta Crystallogr Sect F Struct Biol Commun","Acta Crystallogr Sect F Struct Biol Cryst Commun"],"accepted":{"date-parts":[[2022,10,5]]},"published-print":{"date-parts":[[2022,11,1]]},"abstract":"<jats:p>\n                    Carbonic anhydrases (CAs) are drug targets for a variety of diseases. While many clinically relevant CA inhibitors are sulfonamide-based, novel CA inhibitors are being developed that incorporate alternative zinc-binding groups, such as carboxylic acid moieties, to develop CA isoform-specific inhibitors. Here, the X-ray crystal structure of human CA II (hCA II) in complex with the carboxylic acid ibuprofen [2-(4-isobutylphenyl)propanoic acid, a common over-the-counter nonsteroidal anti-inflammatory drug] is reported to 1.54\u2005\u00c5 resolution. The binding of ibuprofen is overlaid with the structures of other carboxylic acids in complex with hCA II to compare their inhibition mechanisms by direct or indirect (via a water) binding to the active-site zinc. Additionally, enzyme-inhibition assays using ibuprofen, nicotinic acid and ferulic acid were performed with hCA II to determine their IC\n                    <jats:sub>50<\/jats:sub>\n                    values and were compared with those of other carboxylic acid binders. This study discusses the potential development of CA inhibitors utilizing the carboxylic acid moiety.\n                  <\/jats:p>","DOI":"10.1107\/s2053230x22009761","type":"journal-article","created":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T11:33:04Z","timestamp":1665747184000},"page":"395-402","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":4,"title":["Ibuprofen: a weak inhibitor of carbonic anhydrase II"],"prefix":"10.1107","volume":"78","author":[{"given":"Jacob","family":"Combs","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/032db5x82","id-type":"ROR","asserted-by":"publisher"}],"department":["Department of Biochemistry and Molecular Biology, College of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Andring","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/032db5x82","id-type":"ROR","asserted-by":"publisher"}],"department":["Department of Biochemistry and Molecular Biology, College of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"McKenna","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/032db5x82","id-type":"ROR","asserted-by":"publisher"}],"department":["Department of Biochemistry and Molecular Biology, College of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"329","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"no5196_bb2","doi-asserted-by":"crossref","first-page":"527","DOI":"10.3390\/biom10040527","volume":"10","author":"Andring","year":"2020","journal-title":"Biomolecules"},{"key":"no5196_bb3","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1021\/bi902007b","volume":"49","author":"Avvaru","year":"2010","journal-title":"Biochemistry"},{"key":"no5196_bb4","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/nsb1203-980","volume":"10","author":"Berman","year":"2003","journal-title":"Nat. Struct. Mol. Biol."},{"key":"no5196_bb5","doi-asserted-by":"crossref","first-page":"S68","DOI":"10.1038\/sj.bjp.0707528","volume":"153","author":"Bodor","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"no5196_bb6","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1080\/14756366.2022.2053526","volume":"37","author":"Bonardi","year":"2022","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"no5196_bb7","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1107\/S1399004714007457","volume":"70","author":"Boone","year":"2014","journal-title":"Acta Cryst. D"},{"key":"no5196_bb8","doi-asserted-by":"crossref","first-page":"e202200148","DOI":"10.1002\/cmdc.202200148","volume":"17","author":"Bozdag","year":"2022","journal-title":"ChemMedChem"},{"key":"no5196_bb9","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.bmc.2013.11.016","volume":"22","author":"Bozdag","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"no5196_bb10","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1021\/acs.jmedchem.9b01669","volume":"63","author":"Bua","year":"2020","journal-title":"J. Med. Chem."},{"key":"no5196_bb11","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1021\/acsmedchemlett.7b00229","volume":"8","author":"Cadoni","year":"2017","journal-title":"ACS Med. Chem. Lett."},{"key":"no5196_bb12","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/bs.mie.2020.01.003","volume":"634","author":"Combs","year":"2020","journal-title":"Methods Enzymol."},{"key":"no5196_bb13","first-page":"898","volume":"35","author":"Cooper","year":"1977","journal-title":"J. Oral Surg."},{"key":"no5196_bb14","unstructured":"Dean, L. (2005). Blood Groups and Red Cell Antigens, ch. 1. Bethesda: National Center for Biotechnology Information."},{"key":"no5196_bb15","first-page":"1370","volume":"110","author":"Dornan","year":"1974","journal-title":"Can. Med. Assoc. J."},{"key":"no5196_bb16","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Cryst. D"},{"key":"no5196_bb17","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1107\/S0907444913000061","volume":"69","author":"Evans","year":"2013","journal-title":"Acta Cryst. D"},{"key":"no5196_bb18","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1021\/bi901995n","volume":"49","author":"Fisher","year":"2010","journal-title":"Biochemistry"},{"key":"no5196_bb19","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1107\/S1744309109013086","volume":"65","author":"Fisher","year":"2009","journal-title":"Acta Cryst. F"},{"key":"no5196_bb37","doi-asserted-by":"crossref","unstructured":"Frost, S. C. & McKenna, R. (2013). Carbonic Anhydrase: Mechanism, Regulation, Links to Disease, and Industrial Applications. Dordrecht: Springer.","DOI":"10.1007\/978-94-007-7359-2"},{"key":"no5196_bb20","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/BF01972851","volume":"27","author":"Geisslinger","year":"1989","journal-title":"Agents Actions"},{"key":"no5196_bb21","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1107\/S0907444909047337","volume":"66","author":"Kabsch","year":"2010","journal-title":"Acta Cryst. D"},{"key":"no5196_bb22","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1042\/bj0341163","volume":"34","author":"Keilin","year":"1940","journal-title":"Biochem. J."},{"key":"no5196_bb23","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/chem.201503748","volume":"22","author":"Langella","year":"2016","journal-title":"Chem. Eur. J."},{"key":"no5196_bb24","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1021\/ci200227u","volume":"51","author":"Laskowski","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"no5196_bb1","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1107\/S2059798319011471","volume":"75","author":"Liebschner","year":"2019","journal-title":"Acta Cryst. D"},{"key":"no5196_bb25","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1107\/S2053230X18018344","volume":"75","author":"Lomelino","year":"2019","journal-title":"Acta Cryst. F"},{"key":"no5196_bb26","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.3390\/ijms17071150","volume":"17","author":"Lomelino","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"no5196_bb27","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1152\/physrev.1967.47.4.595","volume":"47","author":"Maren","year":"1967","journal-title":"Physiol. Rev."},{"key":"no5196_bb28","doi-asserted-by":"crossref","first-page":"5259","DOI":"10.1039\/c2cc32013d","volume":"48","author":"Martin","year":"2012","journal-title":"Chem. Commun."},{"key":"no5196_bb29","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1021\/acs.jmedchem.0c02077","volume":"64","author":"Mboge","year":"2021","journal-title":"J. Med. Chem."},{"key":"no5196_bb30","doi-asserted-by":"crossref","first-page":"4893","DOI":"10.1021\/ja01167a012","volume":"72","author":"Miller","year":"1950","journal-title":"J. Am. Chem. Soc."},{"key":"no5196_bb31","doi-asserted-by":"crossref","first-page":"7210","DOI":"10.1016\/j.bmc.2013.08.033","volume":"21","author":"Pinard","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"no5196_bb33","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/j.1432-1033.1975.tb02449.x","volume":"59","author":"Steiner","year":"1975","journal-title":"Eur. J. Biochem."},{"key":"no5196_bb34","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrd2467","volume":"7","author":"Supuran","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"no5196_bb35","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3109\/14756366.2015.1122001","volume":"31","author":"Supuran","year":"2016","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"no5196_bb36","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/med.10025","volume":"23","author":"Supuran","year":"2003","journal-title":"Med. Res. Rev."},{"key":"no5196_bb38","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0378-1119(92)90498-E","volume":"117","author":"Tanhauser","year":"1992","journal-title":"Gene"},{"key":"no5196_bb39","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/0006-291X(64)90445-0","volume":"14","author":"Tashian","year":"1964","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"no5196_bb41","doi-asserted-by":"crossref","first-page":"955","DOI":"10.3109\/14756366.2014.1001754","volume":"30","author":"Uda","year":"2015","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"no5196_bb42","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1021\/acs.jmedchem.1c01906","volume":"65","author":"Vannozzi","year":"2022","journal-title":"J. Med. Chem."},{"key":"no5196_bb43","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1107\/S0907444910045749","volume":"67","author":"Winn","year":"2011","journal-title":"Acta Cryst. D"},{"key":"no5196_bb44","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1021\/acs.jmedchem.5b01940","volume":"59","author":"Woods","year":"2016","journal-title":"J. Med. Chem."},{"key":"no5196_bb45","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1159\/000491755","volume":"31","author":"Zdu\u0144ska","year":"2018","journal-title":"Skin Pharmacol. Physiol."}],"container-title":["Acta Crystallographica Section F Structural Biology Communications"],"original-title":[],"link":[{"URL":"https:\/\/journals.iucr.org\/f\/issues\/2022\/11\/00\/no5196\/no5196.pdf","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.iucr.org\/f\/issues\/2022\/11\/00\/no5196\/no5196.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T06:11:12Z","timestamp":1736748672000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.iucr.org\/paper?S2053230X22009761"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,14]]},"references-count":43,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["S2053230X22009761"],"URL":"https:\/\/doi.org\/10.1107\/s2053230x22009761","relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.2210\/pdb8dj9\/pdb","asserted-by":"subject"}]},"ISSN":["2053-230X"],"issn-type":[{"value":"2053-230X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,14]]},"assertion":[{"value":"Acta Crystallographica Section F: Structural Biology Communications","order":0,"name":"journal","label":"Publication","explanation":{"URL":"https:\/\/journals.iucr.org\/f"},"group":{"name":"general","label":"General"}},{"value":"research communications","order":1,"name":"content_type","label":"Content type","explanation":{"URL":"https:\/\/journals.iucr.org\/f\/services\/notesforauthors.html"},"group":{"name":"general","label":"General"}},{"value":"Available","URL":"https:\/\/scripts.iucr.org\/cgi-bin\/citedin?no5196","order":2,"name":"article_metrics","label":"Article metrics","group":{"name":"general","label":"General"}},{"value":"Yes","order":0,"name":"peer_reviewed","label":"Peer reviewed","group":{"name":"peer_review","label":"Peer review"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review process","group":{"name":"peer_review","label":"Peer review"}},{"value":"5 August 2022","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication history"}},{"value":"5 October 2022","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication history"}},{"value":"14 October 2022","order":2,"name":"published_online","label":"Published online","group":{"name":"publication_history","label":"Publication history"}},{"value":"This article has supporting information","name":"supplementary_materials","label":"Supplementary materials","explanation":{"URL":"https:\/\/scripts.iucr.org\/cgi-bin\/sendsup?no5196"}},{"value":"\u00a9 Jacob Combs\n                      et al.","order":0,"name":"copyright","label":"Copyright","explanation":{"URL":"https:\/\/journals.iucr.org\/services\/copyrightpolicy.html"},"group":{"name":"copyright_and_licensing","label":"Copyright and licencing"}},{"value":"IUCr licence to publish","order":1,"name":"license","label":"Licence","explanation":{"URL":"https:\/\/journals.iucr.org\/copyright\/licencetopublish.html"},"group":{"name":"copyright_and_licencing","label":"Copyright and licencing"}}]}}