The ferritin-like superfamily (FLSF) is a class of proteins that contain a diiron active site and participate in important biochemical pathways, including fatty-acid desaturation and the formation of deoxyribonucleotides. The canonical FLSF sequence contains four carboxylate and two histidine metal-binding ligands in the active site. However, the rubrerythrins (Rbr) and symerythrin contain one and two additional carboxylate residues, respectively, in their active sites. Interestingly, these proteins also exhibit enhanced reactivity with hydrogen peroxide relative to other members of the FLSF, but the correlation between the additional carboxylate residues and the altered functionality is currently not well understood. To investigate this phenomenon, models for Rbr and Sym were created based on G4DFsc, which is a small, <i>de novo</i>-designed 4-helix bundle protein that mimics the canonical structure and reactivity of FLSF enzymes. Carboxylate residues, either aspartate (D) or glutamate (E), were introduced at positions G14 and/or G47 to generate Rbr- and Sym-like active sites within the G4DFsc bundle. Metal-binding, protein-folding, and reactivity assays have been used to characterize the geometric and electronic structures of these systems and provide insight into how these particular carboxylate residues in the G4DFsc active site affect its ability to react with hydrogen peroxide.

Creation and characterization of rubrerythrin and symerythrin model proteins

249th National Meeting (2015)

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