Characterization of Protein‐Ligand Interactions in MsrA from E. coli

Abstract

The amino acid methionine is highly susceptible to oxidation via reactive oxygen species, resulting in loss of function in proteins containing oxidized methionines. This loss of protein function has been implicated in numerous neurodegenerative and age‐related diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (Lou Gehrig's Disease), emphysema, and arthritis. The enzyme methionine sulfoxide reductase (MsrA) catalyzes the stereospecific reduction of oxidized methionine in free amino acids, peptides, and proteins, restoring function in the latter. The catalytic mechanism of MsrA has been studied extensively, but less is known about how MsrA is able to recognize its large variety of substrates, from single amino acids or small molecules to oxidized methionines in the context of a protein. Earlier work from our lab using intrinsic and extrinsic fluorescence spectroscopy suggests that the presence of sulfoxide group on a methionine in a target protein enhances existing weak hydrophobic interactions with MsrA. The current study builds on these findings using fluorescence spectroscopy to characterize how MsrA of E. coli recognizes its substrates and repairs specific oxidized methionine residues in an intrinsically‐disordered form of staphylococcal nuclease and a nonapeptide derived from it.Support or Funding InformationThis work was supported by a Research Corporation award (grant number CC5482) to VFS. The Office of Naval Research supported Trident Scholar research by JS. MJW was supported by a Garrigues Program scholarship award.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.