Effect of macromolecular crowding on protein oxidation: Consequences on the rate, extent and oxidation pathways

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dc.article.number102202
dc.catalogadorgjm
dc.contributor.authorFuentes Lemus, Eduardo Felipe
dc.contributor.authorReyes Valenzuela, Juan Sebastián
dc.contributor.authorGamon, Luke F.
dc.contributor.authorLópez Alarcón, Camilo Ignacio
dc.contributor.authorDavies, Michael J.
dc.date.accessioned2024-12-30T16:31:50Z
dc.date.available2024-12-30T16:31:50Z
dc.date.issued2021
dc.description.abstractBiological systems are heterogeneous and crowded environments. Such packed milieus are expected to modulate reactions both inside and outside the cell, including protein oxidation. In this work, we explored the effect of macromolecular crowding on the rate and extent of oxidation of Trp and Tyr, in free amino acids, peptides and proteins. These species were chosen as they are readily oxidized and contribute to damage propagation. Dextran was employed as an inert crowding agent, as this polymer decreases the fraction of volume available to other (macro)molecules. Kinetic analysis demonstrated that dextran enhanced the rate of oxidation of free Trp, and peptide Trp, elicited by AAPH-derived peroxyl radicals. For free Trp, the rates of oxidation were 15.0 ± 2.1 and 30.5 ± 3.4 μM min−1 without and with dextran (60 mg mL−1) respectively. Significant increases were also detected for peptide-incorporated Trp. Dextran increased the extent of Trp consumption (up to 2-fold) and induced short chain reactions. In contrast, Tyr oxidation was not affected by the presence of dextran. Studies on proteins, using SDS-PAGE and LC-MS, indicated that oxidation was also affected by crowding, with enhanced amino acid loss (45% for casein), chain reactions and altered extents of oligomer formation. The overall effects of dextran-mediated crowding were however dependent on the protein structure. Overall, these data indicate that molecular crowding, as commonly encountered in biological systems affect the rates, and extents of oxidation, and particularly of Trp residues, illustrating the importance of appropriate choice of in vitro systems to study biological oxidations.
dc.description.funderMarie Skłodowska-Curie
dc.description.funderFondecyt
dc.description.funderLundbeck Foundation
dc.description.funderEuropean Union's Horizon 2020 research and innovation programme
dc.description.funderNovo Nordisk Foundation
dc.fechaingreso.objetodigital2024-12-30
dc.format.extent16 páginas
dc.fuente.origenScopus
dc.identifier.doi10.1016/j.redox.2021.102202
dc.identifier.issn2213-2317
dc.identifier.scopusidSCOPUS_ID:85120005490
dc.identifier.urihttps://doi.org/10.1016/j.redox.2021.102202
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/89376
dc.information.autorucEscuela de Química; Fuentes Lemus, Eduardo Felipe; 0000-0002-1465-8466; 186720
dc.information.autorucEscuela de Química; Reyes Valenzuela, Juan Sebastián; S/I; 1268701
dc.information.autorucEscuela de Química; López Alarcón, Camilo Ignacio; S/I; 1004308
dc.language.isoen
dc.nota.accesocontenido completo
dc.revistaRedox Biology
dc.rightsacceso abierto
dc.rights.licenseCC BY-NC-ND 4.0 Attribution-NonCommercial-NoDerivatives 4.0 International Deed
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectChain reactions
dc.subjectMacromolecular crowding
dc.subjectPeroxyl radicals
dc.subjectProtein oxidation
dc.subjectTryptophan
dc.subjectTyrosine
dc.subject.ddc510
dc.subject.deweyMatemática física y químicaes_ES
dc.titleEffect of macromolecular crowding on protein oxidation: Consequences on the rate, extent and oxidation pathways
dc.typeartículo
dc.volumen48
sipa.codpersvinculados186720
sipa.codpersvinculados1268701
sipa.codpersvinculados1004308
sipa.trazabilidadSCOPUS;21-03-2022
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