{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T11:05:06Z","timestamp":1784027106892,"version":"3.55.0"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/X001032\/1"],"award-info":[{"award-number":["BB\/X001032\/1"]}],"id":[{"id":"10.13039\/501100000268","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":[[2025,3]]},"abstract":"<jats:p>\n                    Angiotensin\u20101\u2010converting enzyme (ACE) is a zinc\u2010dependent carboxypeptidase of therapeutic interest for the treatment of hypertension, inflammation and fibrosis. It consists of two homologous N and C catalytic domains, nACE and cACE, respectively. Unfortunately, the current clinically available ACE inhibitors produce undesirable side effects due to the nonselective inhibition of these domains. Through structure\u2010based drug design, we previously identified a series of diprolyl\u2010derived inhibitors (SG3, SG15, SG16, SG17 and SG18) in an attempt to specifically target nACE. Only one compound, SG16, possessed significant nACEselectivity. The previously determined\n                    <jats:bold>16<\/jats:bold>\n                    \u2010nACE crystal structure (nACE:SG16) suggested interactions with Tyr369 (Phe381 in cACE) are responsible for this selectivity. To better understand the molecular basis for the lack of selectivity in the remaining compounds, we have cocrystallised nACE in complex with SG3, SG15, SG17 and SG18 and cACE in complex with SG3, SG15, SG16 and SG18 and determined their structures at high resolution. Apart from the catalytic residues, these structures further highlight the importance of residues distal to the active site that may play an important role in the design of domain\u2010selective inhibitors of ACE.\n                  <\/jats:p>","DOI":"10.1111\/febs.17384","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T23:59:58Z","timestamp":1736207998000},"page":"1141-1158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Molecular basis of human angiotensin\u20101 converting enzyme inhibition by a series of diprolyl\u2010derived compounds"],"prefix":"10.1111","volume":"292","author":[{"given":"Kyle S.","family":"Gregory","sequence":"first","affiliation":[{"name":"Department of Life Sciences University of Bath  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyles E.","family":"Cozier","sequence":"additional","affiliation":[{"name":"Department of Life Sciences University of Bath  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Fienberg","sequence":"additional","affiliation":[{"name":"Holistic Drug Discovery and Development (H3D) Centre University of Cape Town  Rondebosch South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Chibale","sequence":"additional","affiliation":[{"name":"Holistic Drug Discovery and Development (H3D) Centre University of Cape Town  Rondebosch South Africa"},{"name":"South African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry and Institute of Infectious Disease and Molecular Medicine University of Cape Town  Observatory South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward D.","family":"Sturrock","sequence":"additional","affiliation":[{"name":"Department of Integrative Biomedical Sciences, and Institute of Infectious Disease and Molecular Medicine University of Cape Town  South\u00a0Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-4058","authenticated-orcid":false,"given":"K. 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