Location dependent coordination chemistry and MRI relaxivity, in de novo designed lanthanide coiled coils

Berwick, Matthew R., Slope, Louise N., Smith, Caitlin F., King, Siobhan M., Newton, Sarah L., Gillis, Richard B., Adams, Gary G., Rowe, Arthur J., Harding, Stephen E., Britton, Melanie M. and Peacock, Anna F. A. (2015) Location dependent coordination chemistry and MRI relaxivity, in de novo designed lanthanide coiled coils. Chemical Science, 7 (3). pp. 2207-2216. ISSN 2041-6539

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Herein, we establish for the first time the design principles for lanthanide coordination within coiled coils, and the important consequences of binding site translation. By interrogating design requirements and by systematically translating binding site residues, one can influence coiled coil stability and more importantly, the lanthanide coordination chemistry. A 10 °A binding site translation along a coiled coil, transforms a coordinatively saturated Tb(Asp) ₃(Asn) ₃ site into one in which three exogenous water molecules are coordinated, and in which the Asn layer is no longer essential for binding, Tb(Asp)₃(H₂O ) ₃. This has a profound impact on the relaxivity of the analogous Gd(III) coiled coil, with more than a fourfold increase in the transverse relaxivity (21 to 89 mM⁻¹ s⁻¹), by bringing into play, in addition to the outer sphere mechanism present for all Gd(III) coiled coils, an inner sphere mechanism. Not only do these findings warrant further investigation for possible exploitation as MRI contrast agents, but understanding the impact of binding site translation on coordination chemistry has important repercussions for metal binding site design, taking us an important step closer to the predictable and truly de novo design of metal binding sites, for new functional applications.

Item Type: Article
RIS ID: https://nottingham-repository.worktribe.com/output/768747
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Health Sciences
University of Nottingham, UK > Faculty of Science > School of Biosciences
Identification Number: https://doi.org/10.1039/c5sc04101e
Depositing User: Eprints, Support
Date Deposited: 03 Apr 2017 12:56
Last Modified: 04 May 2020 17:25
URI: https://eprints.nottingham.ac.uk/id/eprint/41718

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