Alterations in the functional properties of post-translationally modified proteins due to the formation of tyrosine dimers
Oxidative stress introduces post-translational modifications into proteins. In some cases, these modifications not only modify the oxidation state of the target protein, but also alter its structural and functional properties. The formation of intra- and inter-chain tyrosine dimers in proteins are an example of post-translational modification that modifies the susceptibility to proteolytic degradation, the stability of the tertiary structure and of any quaternary structures.
These structural changes give the modified proteins altered/new functional properties towards biological targets such as enzymatic systems and receptors.
Numerous studies have detected tyrosine dimers in key proteins in pathologies for which oxidative stress is a cofactor in the pathogenesis, such as Alzheimer's/Parkinsons' disease.
Tyrosine dimers are present in some wheat proteins able to induce an inflammatory response on host macrophages mediated by activation of the TLR4 receptor.
The present project is aimed at clarifying the functional variations produced by the formation of tyrosine dimers in target biological systems.
To support the research, analytical methods will be developed (based on MS/MS spectrometry) for the identification of tyrosines involved in dimers, and the application of molecular docking and molecular dynamics computational methodologies, including virtual screening and inverse virtual screening, for the prediction of functional changes due to the formation of dityrosines.
Keywords - ENGLISH
protein post-traslational modifications, dityrosine, MS/MS spectrometry, virtual screening, inverse virtual screening
Active participants in the research line (PI last author or *)
Mauro Angeletti
Pillar
Human Health
Macroareas in Human Health
Analytical characterization and functionality of biological molecules
Email Address
mauro.angeletti@unicam.it
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