Local Flexibility Facilitates Oxidization of Buried Methionine Residues
Authors: Xu, Kuiran; N. Uversky, Vladimir; Xue, Bin
Source: Protein and Peptide Letters, Volume 19, Number 6, June 2012 , pp. 688-697(10)
Publisher: Bentham Science Publishers
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.
Keywords: Bioinformatics; Disorder score; Flexibility; Intrinsic disorder; Methionine oxidation; Reactive Oxygen Species (ROS); Solvent accessible surface area; atherosclerosis; methionine; muscular dystrophy; neurodegenerative diseases; oxidized bio-molecules
Document Type: Research Article
Affiliations: Department of Molecular Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC7, Tampa Florida 33612-4799.
Publication date: June 1, 2012
- Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.