RT Journal Article T1 Susceptibility of Protein Methionine Oxidation in Response to Hydrogen Peroxide Treatment–Ex Vivo versus In Vitro: A Computational Insight A1 Aledo-Ramos, Juan Carlos A1 Aledo, Pablo K1 Aminoácidos K1 Estrés oxidativo K1 Señalización celular AB Methionine oxidation plays a relevant role in cell signaling. Recently, we built adatabase containing thousands of proteins identified as sulfoxidation targets. Using this resource,we have now developed a computational approach aimed at characterizing the oxidation of humanmethionyl residues. We found that proteins oxidized in both cell-free preparations (in vitro) andinside 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 mitochondrialproteins were preferentially oxidized ex vivo but not in vitro. The nodes corresponding with ex vivoand in vitro oxidized proteins in a network based on gene ontology terms showed an assortativemixing suggesting that ex vivo oxidized proteins shared among them molecular functions andbiological processes. This was further supported by the observation that proteins from the ex vivoset were co-regulated more often than expected by chance. We also investigated the sequenceenvironment of oxidation sites. Glutamate and aspartate were overrepresented in these environmentsregardless the group. In contrast, tyrosine, tryptophan and histidine were clearly avoided but only inthe environments of the ex vivo sites. A hypothetical mechanism of methionine oxidation accountsfor these observations presented. PB MDPI YR 2020 FD 2020-10 LK https://hdl.handle.net/10630/40140 UL https://hdl.handle.net/10630/40140 LA eng NO Aledo, J.C.; Aledo, P. Susceptibility of Protein Methionine Oxidation in Response to Hydrogen Peroxide Treatment–Ex Vivo Versus In Vitro: A Computational Insight. Antioxidants 2020, 9, 987. https://doi.org/10.3390/antiox9100987 DS RIUMA. Repositorio Institucional de la Universidad de Málaga RD 13 abr 2026