{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T19:25:52Z","timestamp":1768073152360,"version":"3.49.0"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/M026647\/1"],"award-info":[{"award-number":["MR\/M026647\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>Angiotensin\u20101\u2010converting enzyme (ACE) is a key enzyme in the renin\u2013angiotensin\u2013aldosterone and kinin systems where it cleaves angiotensin I and bradykinin peptides, respectively. However, ACE also participates in numerous other physiological functions, can hydrolyse many peptide substrates and has various exo\u2010 and endopeptidase activities. ACE achieves this complexity by containing two homologous catalytic domains (N\u2010 and C\u2010domains), which exhibit different substrate specificities. Here, we present the first open conformation structures of ACE N\u2010domain and a unique closed C\u2010domain structure (2.0\u00a0\u00c5) where the C terminus of a symmetry\u2010related molecule is observed inserted into the active\u2010site cavity and binding to the zinc ion. The open native N\u2010domain structure (1.85\u00a0\u00c5) enables comparison with ACE2, a homologue previously observed in open and closed states. An open S<jats:sub>2<\/jats:sub>_S\u2032\u2010mutant N\u2010domain structure (2.80\u00a0\u00c5) includes mutated residues in the S<jats:sub>2<\/jats:sub> and S\u2032 subsites that effect ligand binding, but are distal to the binding site. Analysis of these structures provides important insights into how structural features of the ACE domains are able to accommodate the wide variety of substrates and allow different peptidase activities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Database<\/jats:title><jats:p>The atomic coordinates and structure factors for Open nACE, Open S2_S\u2032\u2010nACE and Native G13\u2010cACE structures have been deposited with codes <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.2210\/pdb6ZPQ\/pdb\">6ZPQ<\/jats:ext-link>, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.2210\/pdb6ZPT\/pdb\">6ZPT<\/jats:ext-link> and <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.2210\/pdb6ZPU\/pdb\">6ZPU<\/jats:ext-link>, respectively, in the RCSB Protein Data Bank, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.pdb.org\">www.pdb.org<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/febs.15601","type":"journal-article","created":{"date-parts":[[2020,10,17]],"date-time":"2020-10-17T07:36:14Z","timestamp":1602920174000},"page":"2238-2256","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Angiotensin\u2010converting enzyme open for business: structural insights into the subdomain dynamics"],"prefix":"10.1111","volume":"288","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2851-0902","authenticated-orcid":false,"given":"Gyles E.","family":"Cozier","sequence":"first","affiliation":[{"name":"Department of Biology and Biochemistry University of Bath Bath UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9905-1438","authenticated-orcid":false,"given":"Lizelle","family":"Lubbe","sequence":"additional","affiliation":[{"name":"Department of Integrative Biomedical Sciences Institute of Infectious Disease and Molecular Medicine University of Cape Town Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2032-7636","authenticated-orcid":false,"given":"Edward D.","family":"Sturrock","sequence":"additional","affiliation":[{"name":"Department of Integrative Biomedical Sciences Institute of Infectious Disease and Molecular Medicine University of Cape Town Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-4058","authenticated-orcid":false,"given":"K. 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