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dc.contributor.authorBaker, Tessa M.
dc.contributor.authorNeidig, Michael L.
dc.contributor.authorNakashige, Toshiki George
dc.contributor.authorNolan, Elizabeth Marie
dc.date.accessioned2018-02-05T16:24:46Z
dc.date.available2018-02-05T16:24:46Z
dc.date.issued2016-10
dc.date.submitted2016-08
dc.identifier.issn2041-6520
dc.identifier.issn2041-6539
dc.identifier.urihttp://hdl.handle.net/1721.1/113419
dc.description.abstractCalprotectin (CP) is an abundant metal-chelating protein involved in host defense, and the ability of human CP to bind Fe(ii) in a calcium-dependent manner was recently discovered. In the present study, near-infrared magnetic circular dichroism spectroscopy is employed to investigate the nature of Fe(ii) coordination at the two transition-metal-binding sites of CP that are a His₃ Asp motif (site 1) and a His₆ motif (site 2). Upon the addition of sub-stoichiometric Fe(ii), a six-coordinate (6C) Fe(ii) center associated with site 2 is preferentially formed in the presence of excess Ca(ii). This site exhibits an exceptionally large ligand field (10D[subscript q] = 11 045 cm⁻¹) for a non-heme Fe(ii) protein. Analysis of CP variants lacking residues of the His₆ motif supports that CP coordinates Fe(ii) at site 2 by employing six His ligands. In the presence of greater than one equiv. of Fe(ii) or upon mutation of the His₆ motif, the metal ion also binds at site 1 of CP to form a five-coordinate (5C) Fe(ii)-His₃ Asp motif that was previously unidentified in this system. Notably, the introduction of His-to-Ala mutations at the His₆ motif results in a mixture of 6C (site 2) and 5C (site 1) signals in the presence of sub-stoichiometric Fe(ii). These results are consistent with a reduced Fe(ii)-binding affinity of site 2 as more weakly coordinating water-derived ligands complete the 6C site. In the absence of Ca(ii), both sites 1 and 2 are occupied upon addition of sub-stoichiometric Fe(ii), and a stronger ligand field is observed for the 5C site. These spectroscopic studies provide further evaluation of a unique non-heme Fe(ii)-His₆ site for metalloproteins and support the notion that Ca(ii) ions influence the Fe(ii)-binding properties of CP.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant P30-ES002109)en_US
dc.publisherRoyal Society of Chemistry (RSC)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1039/C6SC03487Jen_US
dc.rightsCreative Commons Attribution-NonCommercial 4.0 Internationalen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en_US
dc.sourceRoyal Society of Chemistryen_US
dc.titleMagnetic Circular Dichroism Studies of Iron(ii) Binding to Human Calprotectinen_US
dc.typeArticleen_US
dc.identifier.citationBaker, Tessa M. et al. “Magnetic Circular Dichroism Studies of Iron(ii) Binding to Human Calprotectin.” Chemical Science 8, 2 (2017): 1369–1377 © The Royal Society of Chemistryen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.contributor.mitauthorNakashige, Toshiki George
dc.contributor.mitauthorNolan, Elizabeth Marie
dc.relation.journalChemical Scienceen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2018-02-01T13:04:24Z
dspace.orderedauthorsBaker, Tessa M.; Nakashige, Toshiki G.; Nolan, Elizabeth M.; Neidig, Michael L.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-6234-8155
dc.identifier.orcidhttps://orcid.org/0000-0002-6153-8803
mit.licensePUBLISHER_CCen_US


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