{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:39:07Z","timestamp":1791085147249,"version":"4.1.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,4]]},"abstract":"<jats:p>\n                    Albumin is the major transport protein in blood for Zn\n                    <jats:sup>2+<\/jats:sup>\n                    , a metal ion required for physiological processes and recruited by various drugs and toxins. However, the Zn\n                    <jats:sup>2+<\/jats:sup>\n                    -binding site(s) on albumin is ill-defined. We have analyzed the 18 x-ray crystal structures of human albumin in the PDB and identified a potential five-coordinate Zn site at the interface of domains I and II consisting of N ligands from His-67 and His-247 and O ligands from Asn-99, Asp-249, and H\n                    <jats:sub>2<\/jats:sub>\n                    O, which are the same amino acid ligands as those in the zinc enzymes calcineurin, endonucleotidase, and purple acid phosphatase. The site is preformed in unliganded apo-albumin and highly conserved in mammalian albumins. We have used\n                    <jats:sup>111<\/jats:sup>\n                    Cd NMR as a probe for Zn\n                    <jats:sup>2+<\/jats:sup>\n                    binding to recombinant human albumin. We show that His-67 \u2192 Ala (His67Ala) mutation strongly perturbs Cd\n                    <jats:sup>2+<\/jats:sup>\n                    binding, whereas the mutations Cys34Ala, or His39Leu and Tyr84Phe (residues which may H-bond to Cys-34) have no effect. Weak Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    binding to the fifth coordination site of Cd\n                    <jats:sup>2+<\/jats:sup>\n                    was demonstrated. Cd\n                    <jats:sup>2+<\/jats:sup>\n                    binding was dramatically affected by high fatty acid loading of albumin. Analysis of the x-ray structures suggests that fatty acid binding to site 2 triggers a spring-lock mechanism, which disengages the upper (His-67\/Asn-99) and lower (His-247\/Asp-249) halves of the metal site. These findings provide a possible mechanism whereby fatty acids (and perhaps other small molecules) could influence the transport and delivery of zinc in blood.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0436576100","type":"journal-article","created":{"date-parts":[[2003,4,1]],"date-time":"2003-04-01T14:25:08Z","timestamp":1049207108000},"page":"3701-3706","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":174,"title":["Interdomain zinc site on human albumin"],"prefix":"10.1073","volume":"100","author":[{"given":"Alan J.","family":"Stewart","sequence":"first","affiliation":[{"name":"School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, United Kingdom; and Delta Biotechnology Ltd., Castle Court, Castle Boulevard, Nottingham NG7 1FD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia A.","family":"Blindauer","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, United Kingdom; and Delta Biotechnology Ltd., Castle Court, Castle Boulevard, Nottingham NG7 1FD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Berezenko","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, United Kingdom; and Delta Biotechnology Ltd., Castle Court, Castle Boulevard, Nottingham NG7 1FD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darrell","family":"Sleep","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, United Kingdom; and Delta Biotechnology Ltd., Castle Court, Castle Boulevard, Nottingham NG7 1FD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Sadler","sequence":"additional","affiliation":[{"name":"School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, United Kingdom; and Delta Biotechnology Ltd., Castle Court, Castle Boulevard, Nottingham NG7 1FD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,2,21]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr950042j"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1994.tb00500.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007750100251"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi992182j"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)80574-2"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-202-43522"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199606)167:3<539::AID-JCP17>3.0.CO;2-Z"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1385\/BTER:84:1-3:045"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(80)81267-1"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01993964"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(74)90536-0"},{"key":"e_1_3_3_12_2","volume-title":"All 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