Dinuclear iron centers with a bridging hydroxido or oxido ligand form active sites within a variety of metalloproteins. A key feature of these sites is the ability of the protein to control the structures around the Fe centers, which leads to entatic states that are essential for function. To simulate this controlled environment, artificial proteins have been engineered using biotin− streptavidin (Sav) technology in which Fe complexes from adjacent subunits can assemble to form [Fe III −(μ-OH)−Fe III ] cores. The assembly process is promoted by the site-specific localization of the Fe complexes within a subunit through the designed mutation of a tyrosinate side chain to coordinate the Fe centers. An important outcome is that the Sav host can regulate the Fe•••Fe separation, which is known to be important for function in natural metalloproteins. Spectroscopic and structural studies from X-ray diffraction methods revealed uncommonly long Fe•••Fe separations that change by less than 0.3 Å upon the binding of additional bridging ligands. The structural constraints imposed by the protein host on the di-Fe cores are unique and create examples of active sites having entatic states within engineered artificial metalloproteins.
Artificial metalloproteins
(ArMs) have recently gained significant
interest due to their potential to address issues in a broad scope
of applications, including biocatalysis, biotechnology, protein assembly,
and model chemistry. ArMs are assembled by the incorporation of a
non-native metallocofactor into a protein scaffold. This can be achieved
by a number of methods that apply tools of chemical biology, computational
de novo
design, and synthetic chemistry. In this Perspective,
we highlight select systems in the hope of demonstrating the breadth
of ArM design strategies and applications and emphasize how these
systems address problems that are otherwise difficult to do so with
strictly biochemical or synthetic approaches.
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