Reduction of Protein Bound Methionine Sulfoxide by a Periplasmic Dimethyl Sulfoxide Reductase

Area of Science:

• Biochemistry
• Molecular Biology
• Enzymology

Background:

• Methionine (Met) oxidation to methionine sulfoxide (MetO) is a reversible post-translational modification impacting protein function.
• Methionine sulfoxide reductases (MsrA and MsrB) are known enzymes that reduce MetO in proteins.
• Bacterial molybdenum-containing enzymes, like MsrP, also reduce MetO, particularly under oxidative stress.

Purpose of the Study:

• To investigate whether dimethyl sulfoxide (DMSO) reductases can reduce MetO within proteins, not just as a free amino acid.
• To characterize the efficiency of a specific DMSO reductase (DorA from Rhodobacter sphaeroides) in reducing protein-bound MetO.

Main Methods:

• Utilized model oxidized proteins and peptides.
• Employed enzymatic assays and mass spectrometry to analyze MetO reduction.
• Quantified catalytic values for DorA's activity on protein-bound MetO.

Main Results:

• The periplasmic DorA-type DMSO reductase from Rhodobacter sphaeroides efficiently reduces protein-bound MetO.
• DorA's catalytic efficiency for protein-bound MetO is comparable to its activity on free L-MetO and canonical Msrs.
• This represents the fourth identified class of enzymes capable of reducing MetO within proteins.

Conclusions:

• DMSO reductases, specifically DorA, are a novel class of enzymes that can reduce protein-bound MetO.
• The findings suggest a broader enzymatic repertoire for regulating protein oxidation states than previously known.
• This enzyme type is conserved across proteobacteria and actinobacteria, indicating significant biological relevance.