{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T06:28:03Z","timestamp":1782887283664,"version":"3.54.5"},"reference-count":24,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,8,15]]},"abstract":"<jats:p>Cystinyl aminopeptidase has one Zn2+-binding motif and is a member of the M1 aminopeptidase family. Ion modulation of its catalytic activity was studied in membranes of CHO-K1 cells (Chinese-hamster ovary K1 cells) using L-leucine-p-nitroanilide as substrate. The planar bidentate chelators 1,10-phenanthroline and 2,2\u2032-bipyridine inhibited the activity in a concentration-dependent manner with Hill slopes of 3.32\u00b11.78 and 2.10\u00b10.26 respectively. The acetic acid-containing chelators EDTA, EGTA and DTPA (diethylenetriamine-N,N,N\u2032,N\u2033,N\u2033-penta-acetic acid) weakly affected the activity, but they increased the potency of the planar chelators up to a limit, at which Hill slopes became close to unity. Moreover, competition between 1,10-phenanthroline and the substrate only took place in the presence of EDTA. These findings are compatible with a model in which the bidentate chelators inhibit enzyme activity by decreasing the free Zn2+ concentration. By removing a modulatory ion from an allosteric site at the enzyme, the acetic acid-containing chelators facilitate the direct interaction between the bidentate chelators and the catalytic Zn2+. The inhibitory effect of EDTA plus 1,10-phenanthroline could be completely reversed by Zn2+. Ca2+ and Mg2+ increased the potency of Zn2+ for this process. This is expected if they interact with the modulatory site to decrease the sensitivity of the enzyme towards 1,10-phenanthroline. Conversely, the bidendate chelators increased the high-affinity [125I]angiotensin IV binding to the membranes and this was potentiated by the acetic acid-containing chelators. These findings support the concept that high-affinity [125I]angiotensin IV binding, previously referred to as \u2018AT4 receptor binding\u2019, only occurs for the cystinyl aminopeptidase apoenzyme.<\/jats:p>","DOI":"10.1042\/bj20050349","type":"journal-article","created":{"date-parts":[[2005,8,10]],"date-time":"2005-08-10T14:29:33Z","timestamp":1123684173000},"page":"351-357","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Metal ion modulation of cystinyl aminopeptidase"],"prefix":"10.1042","volume":"390","author":[{"given":"Hilde","family":"Laeremans","sequence":"first","affiliation":[{"name":"Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Demaegdt","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"De\u00a0Backer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minh\u00a0T.","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"Kersemans","sequence":"additional","affiliation":[{"name":"Laboratory of Radiopharmacy, Universiteit Gent, Harelbekestraat 72, B-9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvette","family":"Michotte","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Vauquelin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick\u00a0M.\u00a0L.","family":"Vanderheyden","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2005,8,9]]},"reference":[{"key":"2021112213231492300_B1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1074\/jbc.271.1.56","article-title":"Human placental leucine aminopeptidase\/oxytocinase: a new member of type II membrane spanning zinc metallopeptidase family","volume":"271","author":"Rogi","year":"1996","journal-title":"J. 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