{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T19:23:32Z","timestamp":1784661812745,"version":"3.55.0"},"reference-count":53,"publisher":"International Union of Crystallography (IUCr)","issue":"2","license":[{"start":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T00:00:00Z","timestamp":1582243200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"},{"start":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T00:00:00Z","timestamp":1582243200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"}],"content-domain":{"domain":["iucr.org","wiley.com","iucrj.org"],"crossmark-restriction":true},"short-container-title":["IUCrJ","IUCr J","Int Union Crystallogr J","Int Union Cryst J"],"accepted":{"date-parts":[[2020,1,24]]},"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:p>Nitric oxide (NO) promotes vasodilation through the activation of guanylate cyclase, resulting in the relaxation of the smooth muscle vasculature and a subsequent decrease in blood pressure. Therefore, its regulation is of interest for the treatment and prevention of heart disease. An example is pulmonary hypertension which is treated by targeting this NO\/vasodilation pathway. In bacteria, plants and fungi, nitrite (NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup>) is utilized as a source of NO through enzymes known as nitrite reductases. These enzymes reduce NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup>to NO through a catalytic metal ion, often copper. Recently, several studies have shown nitrite reductase activity of mammalian carbonic anhydrase II (CAII), yet the molecular basis for this activity is unknown. Here we report the crystal structure of copper-bound human CAII (Cu\u2013CAII) in complex with NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup>at 1.2\u2005\u00c5 resolution. The structure exhibits Type 1 (T-1) and 2 (T-2) copper centers, analogous to bacterial nitrite reductases, both required for catalysis. The copper-substituted CAII active site is penta-coordinated with a `side-on' bound NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup>, resembling a T-2 center. At the N terminus, several residues that are normally disordered form a porphyrin ring-like configuration surrounding a second copper, acting as a T-1 center. A structural comparison with both apo- (without metal) and zinc-bound CAII (Zn\u2013CAII) provides a mechanistic picture of how, in the presence of copper, CAII, with minimal conformational changes, can function as a nitrite reductase.<\/jats:p>","DOI":"10.1107\/s2052252520000986","type":"journal-article","created":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T09:42:32Z","timestamp":1582191752000},"page":"287-293","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":23,"title":["Structure and mechanism of copper\u2013carbonic anhydrase II: a nitrite reductase"],"prefix":"10.1107","volume":"7","author":[{"given":"Jacob T.","family":"Andring","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chae Un","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"McKenna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"329","published-online":{"date-parts":[[2020,2,21]]},"reference":[{"key":"lz5032_bb1","doi-asserted-by":"crossref","first-page":"H2068","DOI":"10.1152\/ajpheart.00525.2009","volume":"297","author":"Aamand","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"lz5032_bb2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","volume":"66","author":"Adams","year":"2010","journal-title":"Acta Cryst. D"},{"key":"lz5032_bb3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0167-4838(02)00374-6","volume":"1599","author":"An","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"lz5032_bb4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2018.01.015","volume":"117","author":"Andring","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"lz5032_bb5","doi-asserted-by":"crossref","first-page":"12041","DOI":"10.1073\/pnas.0504207102","volume":"102","author":"Antonyuk","year":"2005","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"lz5032_bb7","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1021\/bi902007b","volume":"49","author":"Avvaru","year":"2010","journal-title":"Biochemistry"},{"key":"lz5032_bb8","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-94-007-7359-2_3","volume":"75","author":"Boone","year":"2014","journal-title":"Subcell. Biochem."},{"key":"lz5032_bb9","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1007\/s007750050375","volume":"4","author":"Briganti","year":"1999","journal-title":"J. Biol. Inorg. Chem."},{"key":"lz5032_bb11","doi-asserted-by":"crossref","first-page":"30766","DOI":"10.1074\/jbc.M805353200","volume":"283","author":"Domsic","year":"2008","journal-title":"J. Biol. Chem."},{"key":"lz5032_bb12","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1107\/S0907444902019455","volume":"59","author":"Duda","year":"2003","journal-title":"Acta Cryst. D"},{"key":"lz5032_bb13","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1021\/bi002295z","volume":"40","author":"Duda","year":"2001","journal-title":"Biochemistry"},{"key":"lz5032_bb14","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","volume":"60","author":"Emsley","year":"2004","journal-title":"Acta Cryst. D"},{"key":"lz5032_bb15","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1107\/S0907444913000061","volume":"69","author":"Evans","year":"2013","journal-title":"Acta Cryst. D"},{"key":"lz5032_bb16","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.ccr.2011.10.011","volume":"256","author":"Feng","year":"2012","journal-title":"Coord. Chem. Rev."},{"key":"lz5032_bb17","doi-asserted-by":"crossref","first-page":"9421","DOI":"10.1021\/bi201487b","volume":"50","author":"Fisher","year":"2011","journal-title":"Biochemistry"},{"key":"lz5032_bb10","unstructured":"Frost, S. C. (2014). In Carbonic Anhydrase: Mechanism, Regulation, Links to Disease, and Industrial Applications, edited by S. C. Frost & R. McKenna. Dordrecht: Springer."},{"key":"lz5032_bb18","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.bbrc.2015.07.025","volume":"464","author":"Fukuda","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"lz5032_bb6","doi-asserted-by":"crossref","unstructured":"Garbuz, A. A., Boronovskiy, S. E. & Nartsissov. (2017). J. Phys. Conf. Ser. 917, 042002.","DOI":"10.1088\/1742-6596\/917\/4\/042002"},{"key":"lz5032_bb19","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1107\/S0907444993008790","volume":"50","author":"H\u00e5kansson","year":"1994","journal-title":"Acta Cryst. D"},{"key":"lz5032_bb20","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ab.2018.05.001","volume":"550","author":"Hanff","year":"2018","journal-title":"Anal. Biochem."},{"key":"lz5032_bb21","doi-asserted-by":"crossref","first-page":"9054","DOI":"10.1021\/bi9900166","volume":"38","author":"Hunt","year":"1999","journal-title":"Biochemistry"},{"key":"lz5032_bb22","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1107\/S0907444909047337","volume":"66","author":"Kabsch","year":"2010","journal-title":"Acta Cryst. D"},{"key":"lz5032_bb23","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.1073\/pnas.1520786113","volume":"113","author":"Kim","year":"2016","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"lz5032_bb24","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1107\/S2052252517017626","volume":"5","author":"Kim","year":"2018","journal-title":"IUCrJ"},{"key":"lz5032_bb25","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1021\/ci200227u","volume":"51","author":"Laskowski","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"lz5032_bb26","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1021\/bi5007767","volume":"54","author":"Li","year":"2015","journal-title":"Biochemistry"},{"key":"lz5032_bb55","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1107\/S2059798319011471","volume":"75","author":"Liebschner","year":"2019","journal-title":"Acta Cryst. D"},{"key":"lz5032_bb27","doi-asserted-by":"crossref","first-page":"127","DOI":"10.3390\/ijms17010127","volume":"17","author":"Lionetto","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"lz5032_bb28","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/nrd2466","volume":"7","author":"Lundberg","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"lz5032_bb29","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1111\/j.1432-1033.1992.tb17490.x","volume":"210","author":"Mangani","year":"1992","journal-title":"Eur. J. Biochem."},{"key":"lz5032_bb30","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1146\/annurev.pc.15.100164.001103","volume":"15","author":"Marcus","year":"1964","journal-title":"Annu. Rev. Phys. Chem."},{"key":"lz5032_bb31","doi-asserted-by":"crossref","first-page":"7598","DOI":"10.1021\/ja8091938","volume":"131","author":"Maupin","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"lz5032_bb32","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1006\/abio.2000.4706","volume":"284","author":"McCall","year":"2000","journal-title":"Anal. Biochem."},{"key":"lz5032_bb33","doi-asserted-by":"crossref","first-page":"3979","DOI":"10.1021\/bi0498914","volume":"43","author":"McCall","year":"2004","journal-title":"Biochemistry"},{"key":"lz5032_bb34","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1113\/jphysiol.1933.sp003077","volume":"80","author":"Meldrum","year":"1933","journal-title":"J. Physiol."},{"key":"lz5032_bb35","doi-asserted-by":"crossref","first-page":"3772","DOI":"10.1021\/ac020022z","volume":"74","author":"Moini","year":"2002","journal-title":"Anal. Chem."},{"key":"lz5032_bb36","doi-asserted-by":"crossref","first-page":"5671","DOI":"10.1021\/acs.inorgchem.5b00057","volume":"54","author":"Nettles","year":"2015","journal-title":"Inorg. Chem."},{"key":"lz5032_bb37","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jinorgbio.2015.04.013","volume":"149","author":"Nielsen","year":"2015","journal-title":"J. Inorg. Biochem."},{"key":"lz5032_bb54","doi-asserted-by":"crossref","first-page":"14997","DOI":"10.1074\/jbc.274.21.14997","volume":"274","author":"Nurizzo","year":"1999","journal-title":"J. Biol. Chem."},{"key":"lz5032_bb38","doi-asserted-by":"crossref","first-page":"E1009","DOI":"10.3390\/molecules22061009","volume":"22","author":"Piazzetta","year":"2017","journal-title":"Molecules"},{"key":"lz5032_bb39","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":"lz5032_bb41","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1107\/S0907444904003166","volume":"60","author":"Saito","year":"2004","journal-title":"Acta Cryst. D"},{"key":"lz5032_bb42","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3109\/00365513.2013.864785","volume":"74","author":"Schultze","year":"2014","journal-title":"Scand. J. Clin. Lab. Invest."},{"key":"lz5032_bb43","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S0005-2728(00)00061-X","volume":"1458","author":"Silverman","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"lz5032_bb44","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1021\/ar00145a005","volume":"21","author":"Silverman","year":"1988","journal-title":"Acc. Chem. Res."},{"key":"lz5032_bb45","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1161\/CIRCULATIONAHA.112.107821","volume":"125","author":"Sparacino-Watkins","year":"2012","journal-title":"Circulation"},{"key":"lz5032_bb46","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0021-9258(18)75831-6","volume":"103","author":"Stadie","year":"1933","journal-title":"J. Biol. Chem."},{"key":"lz5032_bb47","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":"lz5032_bb48","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nsb0495-287","volume":"2","author":"Strange","year":"1995","journal-title":"Nat. Struct. Mol. Biol."},{"key":"lz5032_bb49","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrd2467","volume":"7","author":"Supuran","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"lz5032_bb50","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":"lz5032_bb51","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1006\/abio.1998.2991","volume":"267","author":"Thompson","year":"1999","journal-title":"Anal. Biochem."},{"key":"lz5032_bb52","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."}],"updated-by":[{"DOI":"10.1107\/s2052252521000208","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T00:00:00Z","timestamp":1610928000000}}],"container-title":["IUCrJ"],"original-title":[],"link":[{"URL":"http:\/\/journals.iucr.org\/m\/issues\/2020\/02\/00\/lz5032\/lz5032.pdf","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.iucr.org\/m\/issues\/2020\/02\/00\/lz5032\/lz5032.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T11:05:33Z","timestamp":1736766333000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.iucr.org\/paper?S2052252520000986"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,21]]},"references-count":53,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["S2052252520000986"],"URL":"https:\/\/doi.org\/10.1107\/s2052252520000986","relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.1107\/S2052252520000986\/lz5032sup1.pdf","asserted-by":"subject"},{"id-type":"doi","id":"10.2210\/pdb6pdv\/pdb","asserted-by":"subject"},{"id-type":"doi","id":"10.2210\/pdb6pea\/pdb","asserted-by":"subject"}]},"ISSN":["2052-2525"],"issn-type":[{"value":"2052-2525","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,21]]},"assertion":[{"value":"IUCrJ","order":0,"name":"journal","label":"Publication","explanation":{"URL":"http:\/\/www.iucrj.org\/"},"group":{"name":"general","label":"General"}},{"value":"research papers","order":1,"name":"content_type","label":"Content type","explanation":{"URL":"https:\/\/journals.iucr.org\/m\/services\/notesforauthors.html"},"group":{"name":"general","label":"General"}},{"value":"Available","URL":"http:\/\/scripts.iucr.org\/cgi-bin\/citedin?lz5032","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":"30 October 2019","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication history"}},{"value":"24 January 2020","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication history"}},{"value":"21 February 2020","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":"http:\/\/scripts.iucr.org\/cgi-bin\/sendsup?lz5032"}},{"value":"\u00a9 2020 Andringet al.","order":0,"name":"copyright","label":"Copyright","explanation":{"URL":"http:\/\/journals.iucr.org\/services\/copyrightpolicy.html"},"group":{"name":"copyright_and_licencing","label":"Copyright and licencing"}},{"value":"Creative Commons Attribution (CC-BY)","order":1,"name":"license","label":"Licence","explanation":{"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"},"group":{"name":"copyright_and_licencing","label":"Copyright and licencing"}}]}}