Artificial Iron Proteins: Modeling the Active Sites in Non-Heme Dioxygenases

Miller, Kelsey R. and Paretsky, Jonathan D. and Follmer, Alec H. and Heinisch, Tillmann and Mittra, Kaustuv and Gul, Sheraz and Kim, In-Sik and Fuller, Franklin D. and Batyuk, Alexander and Sutherlin, Kyle D. and Brewster, Aaron S. and Bhowmick, Asmit and Sauter, Nicholas K. and Kern, Jan and Yano, Junko and Green, Michael T. and Ward, Thomas R. and Borovik, A. S.. (2020) Artificial Iron Proteins: Modeling the Active Sites in Non-Heme Dioxygenases. Inorganic Chemistry, 59 (9). pp. 6000-6009.

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Official URL: https://edoc.unibas.ch/76520/

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An important class of non-heme dioxygenases contains a conserved Fe binding site that consists of a 2-His-1-carboxylate facial triad. Results from structural biology show that, in the resting state, these proteins are six-coordinate with aqua ligands occupying the remaining three coordination sites. We have utilized biotin-streptavidin (Sav) technology to design new artificial Fe proteins (ArMs) that have many of the same structural features found within active sites of these non-heme dioxygenases. An Sav variant was isolated that contains the S; 112; E mutation, which installed a carboxylate side chain in the appropriate position to bind to a synthetic Fe; II; complex confined within Sav. Structural studies using X-ray diffraction (XRD) methods revealed a facial triad binding site that is composed of two N donors from the biotinylated ligand and the monodentate coordination of the carboxylate from S; 112; E. Two aqua ligands complete the primary coordination sphere of the Fe; II; center with both involved in hydrogen bond networks within Sav. The corresponding Fe; III; protein was also prepared and structurally characterized to show a six-coordinate complex with two exogenous acetato ligands. The Fe; III; protein was further shown to bind an exogenous azido ligand through replacement of one acetato ligand. Spectroscopic studies of the ArMs in solution support the results found by XRD.
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Bioanorganische Chemie (Ward)
UniBasel Contributors:Ward, Thomas R. R.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 May 2021 01:30
Deposited On:04 May 2020 15:17

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