{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:11:43Z","timestamp":1781323903950,"version":"3.54.1"},"reference-count":50,"publisher":"Elsevier BV","issue":"12","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T00:00:00Z","timestamp":1623801600000},"content-version":"vor","delay-in-days":380,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biophysical Journal"],"published-print":{"date-parts":[[2020,6]]},"DOI":"10.1016\/j.bpj.2020.05.006","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T02:58:07Z","timestamp":1589943487000},"page":"2979-2988","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"title":["Toxic and Physiological Metal Uptake and Release by Human Serum Transferrin"],"prefix":"10.1016","volume":"118","author":[{"given":"David J.","family":"Reilley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Jack T.","family":"Fuller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Nechay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Victor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josiah D.","family":"Ruberry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon I.","family":"Mujika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xabier","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastassia N.","family":"Alexandrova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bpj.2020.05.006_bib1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/j.1432-1033.1996.0387r.x","article-title":"Rationalization of the strength of metal binding to human serum transferrin","volume":"242","author":"Li","year":"1996","journal-title":"Eur. J. Biochem"},{"key":"10.1016\/j.bpj.2020.05.006_bib2","doi-asserted-by":"crossref","first-page":"11218","DOI":"10.1021\/ja052768v","article-title":"Ti(IV) binds to human serum transferrin more tightly than does Fe(III)","volume":"127","author":"Tinoco","year":"2005","journal-title":"J.\u00a0Am. Chem. Soc"},{"key":"10.1016\/j.bpj.2020.05.006_bib3","doi-asserted-by":"crossref","first-page":"3444","DOI":"10.1021\/ja068149j","article-title":"Calorimetric, spectroscopic, and model studies provide insight into the transport of Ti(IV) by human serum transferrin","volume":"129","author":"Tinoco","year":"2007","journal-title":"J.\u00a0Am. Chem. Soc"},{"key":"10.1016\/j.bpj.2020.05.006_bib4","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1080\/009841096161078","article-title":"Aluminum toxicokinetics","volume":"48","author":"Exley","year":"1996","journal-title":"J.\u00a0Toxicol. Environ. Health"},{"key":"10.1016\/j.bpj.2020.05.006_bib5","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1039\/C3EM00374D","article-title":"Human exposure to aluminium","volume":"15","author":"Exley","year":"2013","journal-title":"Environ. Sci. Process. Impacts"},{"key":"10.1016\/j.bpj.2020.05.006_bib6","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s00216-004-2596-z","article-title":"Study of titanocene-DNA and molybdenocene-DNA interactions by inductively coupled plasma-atomic emission spectroscopy","volume":"379","author":"Vera","year":"2004","journal-title":"Anal. Bioanal. Chem"},{"key":"10.1016\/j.bpj.2020.05.006_bib7","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0162-0134(00)00198-7","article-title":"Inhibition of human topoisomerase II by the antitumor metallocenes","volume":"83","author":"Mokdsi","year":"2001","journal-title":"J.\u00a0Inorg. Biochem"},{"key":"10.1016\/j.bpj.2020.05.006_bib8","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.2174\/1568026043387449","article-title":"Gallium in cancer treatment","volume":"4","author":"Jakupec","year":"2004","journal-title":"Curr. Top. Med. Chem"},{"key":"10.1016\/j.bpj.2020.05.006_bib9","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1039\/C6CS00860G","article-title":"Using titanium complexes to defeat cancer: the view from the shoulders of titans","volume":"46","author":"Cini","year":"2017","journal-title":"Chem. Soc. Rev"},{"key":"10.1016\/j.bpj.2020.05.006_bib10","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1021\/cr980430w","article-title":"Transferrin as a metal ion mediator","volume":"99","author":"Sun","year":"1999","journal-title":"Chem. Rev"},{"key":"10.1016\/j.bpj.2020.05.006_bib11","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/med.10008","article-title":"Transferrin\/transferrin receptor-mediated drug delivery","volume":"22","author":"Li","year":"2002","journal-title":"Med. Res. Rev"},{"key":"10.1016\/j.bpj.2020.05.006_bib12","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1211\/jpp.59.7.0004","article-title":"Transferrin-conjugated solid lipid nanoparticles for enhanced delivery of quinine dihydrochloride to the brain","volume":"59","author":"Gupta","year":"2007","journal-title":"J.\u00a0Pharm. Pharmacol"},{"key":"10.1016\/j.bpj.2020.05.006_bib13","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0014-4827(89)90293-0","article-title":"Modulation of transferrin receptor expression and function by anti-transferrin receptor antibodies and antibody fragments","volume":"182","author":"Lesley","year":"1989","journal-title":"Exp. Cell Res"},{"key":"10.1016\/j.bpj.2020.05.006_bib14","doi-asserted-by":"crossref","first-page":"14164","DOI":"10.1073\/pnas.93.24.14164","article-title":"Brain drug delivery of small molecules using immunoliposomes","volume":"93","author":"Huwyler","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bpj.2020.05.006_bib15","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.ejpb.2008.08.021","article-title":"Transferrin- and transferrin-receptor-antibody-modified nanoparticles enable drug delivery across the blood-brain barrier (BBB)","volume":"71","author":"Ulbrich","year":"2009","journal-title":"Eur. J. Pharm. Biopharm"},{"key":"10.1016\/j.bpj.2020.05.006_bib16","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nature10823","article-title":"Structural basis for iron piracy by pathogenic Neisseria","volume":"483","author":"Noinaj","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.bpj.2020.05.006_bib17","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1073\/pnas.80.8.2258","article-title":"pH and the recycling of transferrin during receptor-mediated endocytosis","volume":"80","author":"Dautry-Varsat","year":"1983","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bpj.2020.05.006_bib18","doi-asserted-by":"crossref","first-page":"8002","DOI":"10.1016\/S0021-9258(18)92931-5","article-title":"Binding to cellular receptors results in increased iron release from transferrin at mildly acidic pH","volume":"266","author":"Sipe","year":"1991","journal-title":"J.\u00a0Biol. Chem"},{"key":"10.1016\/j.bpj.2020.05.006_bib19","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1006\/jmbi.1998.1787","article-title":"The nature of ligand-induced conformational change in transferrin in solution. An investigation using X-ray scattering, XAFS and site-directed mutants","volume":"279","author":"Grossmann","year":"1998","journal-title":"J.\u00a0Mol. Biol"},{"key":"10.1016\/j.bpj.2020.05.006_bib20","doi-asserted-by":"crossref","first-page":"7919","DOI":"10.1021\/bi980355j","article-title":"Two high-resolution crystal structures of the recombinant N-lobe of human transferrin reveal a structural change implicated in iron release","volume":"37","author":"MacGillivray","year":"1998","journal-title":"Biochemistry"},{"key":"10.1016\/j.bpj.2020.05.006_bib21","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1021\/bi0353631","article-title":"Redox properties of human transferrin bound to its receptor","volume":"43","author":"Dhungana","year":"2004","journal-title":"Biochemistry"},{"key":"10.1016\/j.bpj.2020.05.006_bib22","doi-asserted-by":"crossref","first-page":"9704","DOI":"10.1021\/bi990134t","article-title":"Dual role of Lys206-Lys296 interaction in human transferrin N-lobe: iron-release trigger and anion-binding site","volume":"38","author":"He","year":"1999","journal-title":"Biochemistry"},{"key":"10.1016\/j.bpj.2020.05.006_bib23","doi-asserted-by":"crossref","first-page":"13696","DOI":"10.1021\/bi980318s","article-title":"Iron release is reduced by mutations of lysines 206 and 296 in recombinant N-terminal half-transferrin","volume":"37","author":"Steinlein","year":"1998","journal-title":"Biochemistry"},{"key":"10.1016\/j.bpj.2020.05.006_bib24","doi-asserted-by":"crossref","first-page":"13089","DOI":"10.1073\/pnas.1105786108","article-title":"How the binding of human transferrin primes the transferrin receptor potentiating iron release at endosomal pH","volume":"108","author":"Eckenroth","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bpj.2020.05.006_bib25","doi-asserted-by":"crossref","first-page":"13978","DOI":"10.1021\/bi9812064","article-title":"Ligand-induced conformational change in transferrins: crystal structure of the open form of the N-terminal half-molecule of human transferrin","volume":"37","author":"Jeffrey","year":"1998","journal-title":"Biochemistry"},{"key":"10.1016\/j.bpj.2020.05.006_bib26","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.bbagen.2011.06.003","article-title":"Kinetics of iron release from transferrin bound to the transferrin receptor at endosomal pH","volume":"1820","author":"Steere","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.bpj.2020.05.006_bib27","doi-asserted-by":"crossref","first-page":"5659","DOI":"10.1021\/jacs.6b01966","article-title":"Unusual synergism of transferrin and citrate in the regulation of Ti(IV) speciation, transport, and toxicity","volume":"138","author":"Tinoco","year":"2016","journal-title":"J.\u00a0Am. Chem. Soc"},{"key":"10.1016\/j.bpj.2020.05.006_bib28","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s00775-018-1557-5","article-title":"The role of citrate, lactate and transferrin in determining titanium release from surgical devices into human serum","volume":"23","author":"Curtin","year":"2018","journal-title":"J.\u00a0Biol. Inorg. Chem"},{"key":"10.1016\/j.bpj.2020.05.006_bib29","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1107\/S0907444907000182","article-title":"Structures of two mutants that probe the role in iron release of the dilysine pair in the N-lobe of human transferrin","volume":"63","author":"Baker","year":"2007","journal-title":"Acta Crystallogr. D Biol. Crystallogr"},{"key":"10.1016\/j.bpj.2020.05.006_bib30","doi-asserted-by":"crossref","first-page":"7017","DOI":"10.1021\/bi300584p","article-title":"Molecular dynamics simulations of iron- and aluminum-loaded serum transferrin: protonation of Tyr188 is necessary to prompt metal release","volume":"51","author":"Mujika","year":"2012","journal-title":"Biochemistry"},{"key":"10.1016\/j.bpj.2020.05.006_bib31","doi-asserted-by":"crossref","first-page":"3485","DOI":"10.1016\/S0006-3495(03)74769-9","article-title":"A computational study of the open and closed forms of the N-lobe human serum transferrin apoprotein","volume":"85","author":"Rinaldo","year":"2003","journal-title":"Biophys. J"},{"key":"10.1016\/j.bpj.2020.05.006_bib32","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1016\/j.jinorgbio.2011.07.019","article-title":"A QM\/MM study of the complexes formed by aluminum and iron with serum transferrin at neutral and acidic pH","volume":"105","author":"Mujika","year":"2011","journal-title":"J.\u00a0Inorg. Biochem"},{"key":"10.1016\/j.bpj.2020.05.006_bib33","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.bpj.2012.06.024","article-title":"Hybrid dynamics simulation engine for metalloproteins","volume":"103","author":"Sparta","year":"2012","journal-title":"Biophys. J"},{"key":"10.1016\/j.bpj.2020.05.006_bib34","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.str.2008.03.013","article-title":"Ab initio folding of proteins with all-atom discrete molecular dynamics","volume":"16","author":"Ding","year":"2008","journal-title":"Structure"},{"key":"10.1016\/j.bpj.2020.05.006_bib35","doi-asserted-by":"crossref","first-page":"5884","DOI":"10.1021\/acs.jpcb.6b00997","article-title":"Histone deacetylase 8: characterization of physiological divalent metal catalysis","volume":"120","author":"Nechay","year":"2016","journal-title":"J.\u00a0Phys. Chem. B"},{"key":"10.1016\/j.bpj.2020.05.006_bib36","doi-asserted-by":"crossref","first-page":"10649","DOI":"10.1021\/jp302771n","article-title":"Why urease is a di-nickel enzyme whereas the CcrA \u03b2-lactamase is a di-zinc enzyme","volume":"116","author":"Valdez","year":"2012","journal-title":"J.\u00a0Phys. Chem. B"},{"key":"10.1016\/j.bpj.2020.05.006_bib37","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1016\/j.jmb.2013.05.001","article-title":"Metal-dependent activity of Fe and Ni acireductone dioxygenases: how two electrons reroute the catalytic pathway","volume":"425","author":"Sparta","year":"2013","journal-title":"J.\u00a0Mol. Biol"},{"key":"10.1016\/j.bpj.2020.05.006_bib38","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.cplett.2014.04.055","article-title":"Co2+ acireductone dioxygenase: Fe2+ mechanism, Ni2+ mechanism, or something else?","volume":"604","author":"Valdez","year":"2014","journal-title":"Chem. Phys. Lett"},{"key":"10.1016\/j.bpj.2020.05.006_bib39","doi-asserted-by":"crossref","first-page":"4112","DOI":"10.1016\/j.jmb.2014.07.016","article-title":"Cu,Zn-superoxide dismutase without Zn is folded but catalytically inactive","volume":"426","author":"Nedd","year":"2014","journal-title":"J.\u00a0Mol. Biol"},{"key":"10.1016\/j.bpj.2020.05.006_bib40","doi-asserted-by":"crossref","first-page":"5010","DOI":"10.1039\/C7SC01301A","article-title":"Quantified electrostatic preorganization in enzymes using the geometry of the electron charge density","volume":"8","author":"Morgenstern","year":"2017","journal-title":"Chem. Sci. (Camb.)"},{"key":"10.1016\/j.bpj.2020.05.006_bib41","doi-asserted-by":"crossref","first-page":"31744","DOI":"10.1039\/C6CP02247B","article-title":"Predictive methods for computational metalloenzyme redesign - a test case with carboxypeptidase A","volume":"18","author":"Valdez","year":"2016","journal-title":"Phys. Chem. Chem. Phys"},{"key":"10.1016\/j.bpj.2020.05.006_bib42","doi-asserted-by":"crossref","first-page":"4534","DOI":"10.1021\/acs.jpcb.9b02893","article-title":"Uncovered dynamic coupling resolves the ambiguous mechanism of phenylalanine hydroxylase oxygen binding","volume":"123","author":"Reilley","year":"2019","journal-title":"J.\u00a0Phys. Chem. B"},{"key":"10.1016\/j.bpj.2020.05.006_bib43","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1021\/ct300712j","article-title":"The role of the flexible L43\u2013S54 protein loop in the CcrA metallo-\u03b2-lactamase in binding structurally dissimilar \u03b2-lactam antibiotics","volume":"9","author":"Valdez","year":"2013","journal-title":"J.\u00a0Chem. Theory Comput"},{"key":"10.1016\/j.bpj.2020.05.006_bib44","series-title":"Turbomole Version 6.6","year":"2014"},{"key":"10.1016\/j.bpj.2020.05.006_bib45","doi-asserted-by":"crossref","first-page":"12129","DOI":"10.1063\/1.1626543","article-title":"Comparative assessment of a new nonempirical density functional: molecules and hydrogen-bonded complexes","volume":"119","author":"Staroverov","year":"2003","journal-title":"J.\u00a0Chem. Phys"},{"key":"10.1016\/j.bpj.2020.05.006_bib46","doi-asserted-by":"crossref","first-page":"154104","DOI":"10.1063\/1.3382344","article-title":"A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu","volume":"132","author":"Grimme","year":"2010","journal-title":"J.\u00a0Chem. Phys"},{"key":"10.1016\/j.bpj.2020.05.006_bib47","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1039\/b508541a","article-title":"Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn: design and assessment of accuracy","volume":"7","author":"Weigend","year":"2005","journal-title":"Phys. Chem. Chem. Phys"},{"key":"10.1016\/j.bpj.2020.05.006_bib48","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1021\/j100007a062","article-title":"Conductor-like screening model for real solvents: a new approach to the quantitative calculation of solvation phenomena","volume":"99","author":"Klamt","year":"1995","journal-title":"J.\u00a0Phys. Chem"},{"key":"10.1016\/j.bpj.2020.05.006_bib49","series-title":"Critical Survey of Stability Constants of EDTA Complexes","author":"Anderegg","year":"1977"},{"key":"10.1016\/j.bpj.2020.05.006_bib50","doi-asserted-by":"crossref","DOI":"10.5402\/2012\/124803","article-title":"Density functional theory study on metal-binding energies for human serum transferrin-metal complexes","volume":"2012","author":"Sakajiri","year":"2012","journal-title":"ISRN Biophysics"}],"container-title":["Biophysical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006349520304021?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006349520304021?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T16:43:20Z","timestamp":1757781800000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006349520304021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6]]},"references-count":50,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["S0006349520304021"],"URL":"https:\/\/doi.org\/10.1016\/j.bpj.2020.05.006","relation":{},"ISSN":["0006-3495"],"issn-type":[{"value":"0006-3495","type":"print"}],"subject":[],"published":{"date-parts":[[2020,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Toxic and Physiological Metal Uptake and Release by Human Serum Transferrin","name":"articletitle","label":"Article Title"},{"value":"Biophysical Journal","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bpj.2020.05.006","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Biophysical Society.","name":"copyright","label":"Copyright"}]}}