A Noncanonical Proximal Heme Ligand Affords an Efficient Peroxidase in a Globin Fold
Abstract
Expanding the range of genetically encoded metal coordination environments accessible within tunable protein scaffolds presents excellent opportunities for the creation of metalloenzymes with augmented properties and novel activities. Here, we demonstrate that installation of a noncanonical Nδ-methyl histidine (NMH) as the proximal heme ligand in the oxygen binding protein myoglobin (Mb) leads to substantial increases in heme redox potential and promiscuous peroxidase activity. Structural characterization of this catalytically modified myoglobin variant (Mb NMH) revealed significant changes in the proximal pocket, including alterations to hydrogen-bonding interactions involving the prosthetic porphyrin cofactor. Further optimization of Mb NMH via a combination of rational modification and several rounds of laboratory evolution afforded efficient peroxidase biocatalysts within a globin fold, with activities comparable to those displayed by nature’s peroxidases. Show more
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https://doi.org/10.3929/ethz-b-000242960Publication status
publishedExternal links
Journal / series
Journal of the American Chemical SocietyVolume
Pages / Article No.
Publisher
American Chemical SocietyOrganisational unit
03492 - Hilvert, Donald (emeritus) / Hilvert, Donald (emeritus)
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