Nickel Sequestration by the Host-Defense Protein Human Calprotectin.
The human innate immune protein calprotectin (CP, S100A8/S100A9 oligomer, calgranulin A/calgranulin B oligomer, MRP-8/MRP-14 oligomer) chelates a number of first-row transition metals, including Mn(II), Fe(II), and Zn(II), and can withhold these essential nutrients from microbes. Here we elucidate t...
| Publicado en: | Journal of the American Chemical Society Vol. 139; no. 26; pp. 8828 - 8837 |
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| Autores principales: | , , , |
| Formato: | Artículo |
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American Chemical Society
7/5/2017
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| Materias: | |
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=123963126&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 123963126 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 7/5/2017 vid: 139 iid: 26 pid: 997 pub: American Chemical Society artinfo: ui: 123963126 10.1021/jacs.7b01212 ppf: 8828 ppct: 9 formats: tig: atl: Nickel Sequestration by the Host-Defense Protein Human Calprotectin. aug: au: Nakashige, Toshiki G. Zygiel, Emily M. Drennan, Catherine L. Nolan, Elizabeth M. affil: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States su: Sequestration (Chemistry) Lectins Coordinate covalent bond Chelation Staphylococcus aureus Enzyme inhibitors Urease sug: subj: Sequestration (Chemistry) Lectins Coordinate covalent bond Chelation Staphylococcus aureus Enzyme inhibitors Urease ab: The human innate immune protein calprotectin (CP, S100A8/S100A9 oligomer, calgranulin A/calgranulin B oligomer, MRP-8/MRP-14 oligomer) chelates a number of first-row transition metals, including Mn(II), Fe(II), and Zn(II), and can withhold these essential nutrients from microbes. Here we elucidate the Ni(II) coordination chemistry of human CP. We present a 2.6-Šcrystal structure of Ni(II)- and Ca(II)-bound CP, which reveals that CP binds Ni(II) ions at both its transition-metal-binding sites: the HisAsp motif (site 1) and the His motif (site 2). Further biochemical studies establish that coordination of Ni(II) at the hexahistidine site is thermodynamically preferred over Zn(II). We also demonstrate that CP can sequester Ni(II) from two human pathogens, Staphylococcus aureus and Klebsiella pneumoniae, that utilize this metal nutrient during infection, and inhibit the activity of the Ni(II)-dependent enzyme urease in bacterial cultures. In total, our findings expand the biological coordination chemistry of Ni(II)-chelating proteins in nature and provide a foundation for evaluating putative roles of CP in Ni(II) homeostasis at the host-microbe interface and beyond. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2017 holdings: @attributes: islocal: N |
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