Title:Local Flexibility Facilitates Oxidization of Buried Methionine Residues
VOLUME: 19 ISSUE: 6
Author(s):Kuiran Xu, Vladimir N. Uversky and Bin Xue
Affiliation:Department of Molecular Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC7, Tampa Florida 33612-4799.
Keywords:Bioinformatics, Disorder score, Flexibility, Intrinsic disorder, Methionine oxidation, Solvent accessible surface
area, Reactive Oxygen Species (ROS), neurodegenerative diseases, atherosclerosis, muscular dystrophy, oxidized bio-molecules, methionine
Abstract:In proteins, all amino acid residues are susceptible to oxidation by various reactive oxygen species (ROS), with
methionine and cysteine residues being particularly sensitive to oxidation. Methionine oxidation is known to lead to destabilization
and inactivation of proteins, and oxidatively modified proteins can accumulate during aging, oxidative stress,
and in various age-related diseases. Although the efficiency of a given methionine oxidation can depend on its solvent accessibility
(evaluated from a protein structure as the accessible surface area of the corresponding methionine residue),
many experimental results on oxidation rate and oxidation sites cannot be unequivocally explained by the methionine solvent
accessible surface area alone. In order to explore other possible mechanisms, we analyzed a set of seventy-one oxidized
methionines contained in thirty-one proteins by various bioinformatics tools. In which, 41% of the methionines are
exposed, 15% are buried but with various degree of flexibility, and the rest 44% are buried and structured. Buried but
highly flexible methionines can be oxidized. Buried and less flexible methionines can acquire additional local structural
flexibility from flanking regions to facilitate the oxidation. Oxidation of buried and structured methionine can also be
promoted by the oxidation of neighboring methionine that is more exposed and/or flexible. Our data are consistent with
the hypothesis that protein structural flexibility represents another important factor favoring the oxidation process.
