The target specificity of thioredoxin family proteins is determined by electrostatic compatibility
Dissertation, Mathematisch-Naturwissenschaftliche Fakultät der Universität Greifswald, 2021
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Zusammenfassung: | Dissertation, Mathematisch-Naturwissenschaftliche Fakultät der Universität Greifswald, 2021 protein interaction The thioredoxin (Trx) family of proteins comprises many key enzymes in redox signaling, that catalyzes specific reversible redox reactions, e.g. dithiol-disulfide exchange reactions, (de-)glutathionylation, trans-nitrosylation, or peroxide reduction. With the analysis of a large number of proteins, as well as a certain redox couple in [article 1] and [article 4], we demonstrated that electrostatic complementarity is the major distinguishing feature that controls the specific interactions of Trxs with their target proteins. The primary aim of this work was to determine the importance of this specific interaction and the prediction, modulation, and engineering of functional redox interactions of Trx family proteins. To understand the role of electrostatic complementarity for the mammalian Trx1-TrxR complex, we generated more than 20 hTrx1 mutants and systematically engineered the electrostatic potential within and outside the contact area with TrxR [article 1]. The effects of these specific alterations distributed all over the protein surface were analyzed by enzyme kinetics, differential scanning fluorimetry (DSF), circular dichroism (CD) spectroscopy, and MD simulations. Trx family proteins have a broad and very distinct substrate specificity, which is a prerequisite for redox switching. In [article 4], we comprehensively compared the classification of various redoxins from all kingdoms of life based on their similarity in amino acid sequence, tertiary structure, and ... |
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Beschreibung: | Literaturverzeichnis: Seite 23-36. - Literaturangaben |
Beschreibung: | i, 117 Seiten Illustrationen (teilweise farbig), Diagramme (teilweise farbig) |