An efficient, step-economical strategy for the design of functional metalloproteins.

ABSTRACT: The bottom-up design and construction of functional metalloproteins remains a formidable task in biomolecular design. Although numerous strategies have been used to create new metalloproteins, pre-existing knowledge of the tertiary and quaternary protein structure is often required to generate suitable platforms for robust metal coordination and activity. Here we report an alternative and easily implemented approach (metal active sites by covalent tethering or MASCoT) in which folded protein building blocks are linked by a single disulfide bond to create diverse metal coordination environments within evolutionarily naive protein-protein interfaces. Metalloproteins generated using this strategy uniformly bind a wide array of first-row transition metal ions (Mn^II, Fe^II,

SUBMITTER: Rittle J 

PROVIDER: S-EPMC6483823 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature