Susceptibility of Protein Methionine Oxidation in Response to Hydrogen Peroxide Treatment–Ex Vivo Versus In Vitro: A Computational Insight

Abstract

Methionine oxidation plays a relevant role in cell signaling. Recently, we built a database containing thousands of proteins identified as sulfoxidation targets. Using this resource, we have now developed a computational approach aimed at characterizing the oxidation of human methionyl residues. We found that proteins oxidized in both cell-free preparations (in vitro) and inside living cells (ex vivo) were enriched in methionines and intrinsically disordered regions. However, proteins oxidized ex vivo tended to be larger and less abundant than those oxidized in vitro. Another distinctive feature was their subcellular localizations. Thus, nuclear and mitochondrial proteins were preferentially oxidized ex vivo but not in vitro. The nodes corresponding with ex vivo and in vitro oxidized proteins in a network based on gene ontology terms showed an assortative mixing suggesting that ex vivo oxidized proteins shared among them molecular functions and biological processes. This was further supported by the observation that proteins from the ex vivo set were co-regulated more often than expected by chance. We also investigated the sequence environment of oxidation sites. Glutamate and aspartate were overrepresented in these environments regardless the group. In contrast, tyrosine, tryptophan and histidine were clearly avoided but only in the environments of the ex vivo sites. A hypothetical mechanism of methionine oxidation accounts for these observations presented.

Multi-Omics Analysis of Anti-Inflammatory Action of Alkaline Extract of the Leaves of Sasa sp.

“…This is consistent with our previous finding that Met-sulfoxide and 5-oxoproline declined during the aggravation of IL1-β-induced HGF inflammation by TiO 2 nanoparticles ( Supplementary Figure S2A,B , cited from [ 15 ]). Since Met-sulfoxide [ 23 , 24 , 25 ] and 5-oxoproline [ 26 , 27 , 28 ] are well-known markers reflecting oxidative stress, SE might have induced the cells to fight against oxidative stress.…”

Phylogenies from unaligned proteomes using sequence environments of amino acid residues

“…It has been shown that every amino acid has a characteristic sequence environment in proteins 41 , 54 . In previous works, we have analyzed the sequence environment (10 residues on each side) around methionine residues in human proteins 42 , 43 , 55 . Thus, and just based on methionine residues, the human proteome can be characterized by a matrix, M , whose elements (m ij ) provide the absolute frequency of the amino acid i at the position j in the environment of methionine residues (Fig.…”

Phylogenies From Unaligned Whole Genomes Using Sequence Environments of Amino Acid Residues

“…The species vector space It has been shown that every amino acid has a characteristic sequence environment in proteins 39,46 . In previous works, we have analyzed the sequence environment (10 residues on each side) around methionine residues in human proteins 40,41,47 . Thus, and just based on methionine residues, the human proteome can be characterized by a matrix, M, whose elements (m ij ) provide the absolute frequency of the amino acid i at the position j in the environment of methionine residues (Figure 1A).…”