{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T20:33:12Z","timestamp":1770841992369,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2012,11,22]],"date-time":"2012-11-22T00:00:00Z","timestamp":1353542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2012,12]]},"abstract":"Human somatic angiotensin\u20101 converting enzyme (ACE<\/jats:styled-content>) is a zinc\u2010dependent exopeptidase, that catalyses the conversion of the decapeptide angiotensin\u00a0I to the octapeptide angiotensin\u00a0II<\/jats:styled-content>, by removing a C\u2010terminal dipeptide. It is the principal component of the renin\u2010angiotensin\u2013aldosterone system that regulates blood pressure. Hence it is an important therapeutic target for the treatment of hypertension and cardiovascular disorders. Here, we report the structures of anACE<\/jats:styled-content>homologue fromDrosophila\u00a0melanogaster<\/jats:italic>(AnCE<\/jats:styled-content>; a proven structural model for the more complex humanACE<\/jats:styled-content>) co\u2010crystallized with mammalian peptide substrates (bradykinin, Thr6<\/jats:sup>\u2013bradykinin, angiotensin\u00a0I and a snake venom peptide inhibitor, bradykinin\u2010potentiating peptide\u2010b). The structures determined at 2\u2010\u00c5 resolution illustrate that both angiotensin\u00a0II<\/jats:styled-content>(the cleaved product of angiotensin\u00a0I by AnCE<\/jats:styled-content>) and bradykinin\u2010potentiating peptide\u2010b bind in an analogous fashion at the active site of AnCE<\/jats:styled-content>, but also exhibit significant differences. In addition, the binding of Arg\u2013Pro\u2013Pro, the cleavage product of bradykinin and Thr6<\/jats:sup>\u2013 bradykinin, provides additional detail of the general peptide binding in AnCE<\/jats:styled-content>. Thus the new structures of AnCE<\/jats:styled-content>complexes presented here improves our understanding of the binding of peptides and the mechanism by which peptides inhibit this family of enzymes.<\/jats:p><\/jats:sec>Database<\/jats:title>The atomic coordinates and structure factors for AnCE<\/jats:styled-content>\u2013Ang\u00a0II<\/jats:styled-content>(code4AA1<\/jats:ext-link>), AnCE<\/jats:styled-content>\u2013BPP<\/jats:styled-content>b (code4AA2<\/jats:ext-link>), AnCE<\/jats:styled-content>\u2013BK<\/jats:styled-content>(code4ASQ<\/jats:ext-link>) and AnCE\u2013Thr6\u2013BK<\/jats:styled-content>(code4ASR<\/jats:ext-link>) complexes have been deposited in the Protein Data Bank,R<\/jats:styled-content>esearchC<\/jats:styled-content>ollaboratory forS<\/jats:styled-content>tructuralB<\/jats:styled-content>ioinformatics,R<\/jats:styled-content>utgersU<\/jats:styled-content>niversity,N<\/jats:styled-content>ewB<\/jats:styled-content>runswick,NJ<\/jats:styled-content>(http:\/\/www.rcsb.org\/<\/jats:ext-link>)<\/jats:p><\/jats:sec>Structured digital abstract<\/jats:title>\u2022\u00a0AnCE<\/jats:ext-link>\u00a0cleaves<\/jats:ext-link>\u00a0Ang I<\/jats:ext-link>\u00a0by\u00a0enzymatic study<\/jats:ext-link>\u00a0(View interaction<\/jats:ext-link>)<\/jats:p>\u2022\u00a0Bradykinin<\/jats:ext-link>\u00a0and\u00a0AnCE<\/jats:ext-link>\u00a0bind<\/jats:ext-link>\u00a0by\u00a0x-ray crystallography<\/jats:ext-link>\u00a0(View interaction<\/jats:ext-link>)<\/jats:p>\u2022\u00a0BPP<\/jats:ext-link>\u00a0and\u00a0AnCE<\/jats:ext-link>\u00a0bind<\/jats:ext-link>\u00a0by\u00a0x-ray crystallography<\/jats:ext-link>\u00a0(View interaction<\/jats:ext-link>)<\/jats:p>\u2022\u00a0AnCE<\/jats:ext-link>\u00a0cleaves<\/jats:ext-link>\u00a0Bradykinin<\/jats:ext-link>\u00a0by\u00a0enzymatic study<\/jats:ext-link>\u00a0(View interaction<\/jats:ext-link>)<\/jats:p>\u2022\u00a0Ang II<\/jats:ext-link>\u00a0and\u00a0AnCE<\/jats:ext-link>\u00a0bind<\/jats:ext-link>\u00a0by\u00a0x-ray crystallography<\/jats:ext-link>\u00a0(View interaction<\/jats:ext-link>)<\/jats:p><\/jats:sec>","DOI":"10.1111\/febs.12038","type":"journal-article","created":{"date-parts":[[2012,10,20]],"date-time":"2012-10-20T16:26:12Z","timestamp":1350750372000},"page":"4525-4534","source":"Crossref","is-referenced-by-count":21,"title":["Structural basis of peptide recognition by the angiotensin\u20101 converting enzyme homologue AnCE<\/scp>fromD<\/scp>rosophila\u00a0melanogaster<\/i>"],"prefix":"10.1111","volume":"279","author":[{"given":"Mohd","family":"Akif","sequence":"first","affiliation":[{"name":"Department of Biology and Biochemistry University of Bath UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey","family":"Masuyer","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry University of Bath UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Bingham","sequence":"additional","affiliation":[{"name":"Faculty of Biological Sciences, School of Biology University of Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward D.","family":"Sturrock","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine University of Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. Elwyn","family":"Isaac","sequence":"additional","affiliation":[{"name":"Faculty of Biological Sciences, School of Biology University of Leeds UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. Ravi","family":"Acharya","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry University of Bath UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,11,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-079611-3.50090-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.51.070182.001435"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1227"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986712799034950"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)31543-6"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)98378-X"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400149200"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.097865"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.8.3656"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118484"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2010.11.001"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/157340809789071155"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1358\/dof.2011.036.01.1537940"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.23.13613"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3180125"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1998.2570599.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2005.05069.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.05.024"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00128-5"},{"key":"e_1_2_7_21_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0022-3565(25)28878-4","article-title":"Characterization of a dipeptide hydrolase (kininase\u00a0II:angiotensin\u00a0I converting enzyme)","volume":"177","author":"Yang HY","year":"1971","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep00717"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2008.11.021"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2990651"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(97)76066-X"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444994003112"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889807021206"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444996012255"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/355472a0"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904019158"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm216"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.1334"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ffebs.12038","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.12038","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/febs.12038","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.12038","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T22:00:41Z","timestamp":1744840841000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.12038"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,22]]},"references-count":31,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["10.1111\/febs.12038"],"URL":"https:\/\/doi.org\/10.1111\/febs.12038","archive":["Portico"],"relation":{},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,22]]}}}