Oxidation increases the strength of the methionine-aromatic interaction.

Autor: Lewis AK; Department of Biomedical Engineering, University of Minnesota-Twin Cities, Minneapolis, Minnesota, USA., Dunleavy KM; Department of Chemistry and Biochemistry, University of Minnesota-Duluth, Duluth, Minnesota, USA., Senkow TL; Department of Biomedical Engineering, University of Minnesota-Twin Cities, Minneapolis, Minnesota, USA., Her C; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota-Twin Cities, Minneapolis, Minnesota, USA., Horn BT; Department of Chemistry and Biochemistry, University of Minnesota-Duluth, Duluth, Minnesota, USA., Jersett MA; Department of Chemistry and Biochemistry, University of Minnesota-Duluth, Duluth, Minnesota, USA., Mahling R; Department of Chemistry and Biochemistry, University of Minnesota-Duluth, Duluth, Minnesota, USA., McCarthy MR; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota-Twin Cities, Minneapolis, Minnesota, USA., Perell GT; Department of Chemistry, University of Minnesota-Twin Cities, Minneapolis, Minnesota, USA., Valley CC; Department of Biomedical Engineering, University of Minnesota-Twin Cities, Minneapolis, Minnesota, USA., Karim CB; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota-Twin Cities, Minneapolis, Minnesota, USA., Gao J; Department of Chemistry, University of Minnesota-Twin Cities, Minneapolis, Minnesota, USA., Pomerantz WC; Department of Chemistry, University of Minnesota-Twin Cities, Minneapolis, Minnesota, USA., Thomas DD; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota-Twin Cities, Minneapolis, Minnesota, USA., Cembran A; Department of Chemistry and Biochemistry, University of Minnesota-Duluth, Duluth, Minnesota, USA., Hinderliter A; Department of Chemistry and Biochemistry, University of Minnesota-Duluth, Duluth, Minnesota, USA., Sachs JN; Department of Biomedical Engineering, University of Minnesota-Twin Cities, Minneapolis, Minnesota, USA.
Jazyk: angličtina
Zdroj: Nature chemical biology [Nat Chem Biol] 2016 Oct; Vol. 12 (10), pp. 860-6. Date of Electronic Publication: 2016 Aug 22.
DOI: 10.1038/nchembio.2159
Abstrakt: Oxidation of methionine disrupts the structure and function of a range of proteins, but little is understood about the chemistry that underlies these perturbations. Using quantum mechanical calculations, we found that oxidation increased the strength of the methionine-aromatic interaction motif, a driving force for protein folding and protein-protein interaction, by 0.5-1.4 kcal/mol. We found that non-hydrogen-bonded interactions between dimethyl sulfoxide (a methionine analog) and aromatic groups were enriched in both the Protein Data Bank and Cambridge Structural Database. Thermal denaturation and NMR spectroscopy experiments on model peptides demonstrated that oxidation of methionine stabilized the interaction by 0.5-0.6 kcal/mol. We confirmed the biological relevance of these findings through a combination of cell biology, electron paramagnetic resonance spectroscopy and molecular dynamics simulations on (i) calmodulin structure and dynamics, and (ii) lymphotoxin-α binding toTNFR1. Thus, the methionine-aromatic motif was a determinant of protein structural and functional sensitivity to oxidative stress.
Databáze: MEDLINE
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