De novo design of proteins with functional, catalytically active metal centers is a considerable challenge and has typically been achieved using small, parametrically designable alpha-helical peptide assemblies/small proteins. In our goal to build new metalloproteins, we have taken a different approach (inspired by a hypothetical evolutionary route) in which folded, monomeric proteins are used as ligands/synthons for building supramolecular complexes through metal-mediated self-assembly. The interfaces in the resulting protein superstructures are subsequently tailored with covalent, non-covalent or additional metal-coordination interactions for stabilization and incorporation of new metal-based functionalities. This presentation will focus on  artificial metalloproteins and metalloenzymes recently constructed in our lab using this metal-templated design strategy.

Design and evolution of functional metalloprotein assemblies

ACS Fall 2021

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