Structure-functional Characterization of Mammalian Redox Proteins: Methionine sulfoxide reductase B1 (MsrB1), Glutaredoxin domain (Grx) of TGR, and Thioredoxin (Trx)
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This thesis was written at the Department of Biotechnology of Norwegian University of Science and Technology (NTNU) and made as a completion of the three-year PhD program. It summarises the studies of the thiol redox active mammalian enzymes operating within thioredoxin defence system. Aiming to characterize their structural and functional aspects high resolution NMR spectroscopy technique was mainly used along with other complementary techniques. This study covers four research projects dedicated to the following proteins: methionine sulfoxide reductase B1 (MsrB1), thioredoxin (Trx), methionine sulfoxide reductase B (MsrBs), and Grx domain of mouse TGR (Grx). The reduction mechanism of MsrB1, focusing on structural aspects of the intermolecular protein complex formation between MsrB1 and its functional partner Trx was the subject of the first study. Analysis and systematization of the currently available structural data about the key members of the cellular antioxidant defence system, MsrB enzymes, were presented in the second study. Thioredoxin glutathione reductase (TGR) is a member of the mammalian thioredoxin reductase family that has a monothiol glutaredoxin (Grx) domain attached to the thioredoxin reductase module. Grx structure determination and characterization was performed in the third project. MsrB1 contains zinc ion coordinated by four cysteines. Recombinantly expressed in E.coli cells in cobalt-supplemented medium MsrB1 was demonstrated to uptake cobalt ion. Structural studies of cobalt-containing MsrB1 were described in the fourth project.
Has partsDobrovolska, Olena; Rychkov, Georgy; Shumilina, Elena; Nerinovski, Kirill; Schmidt, Alexander; Shabalin, Konstantin; Yakimov, Alexander; Dikiy, Alexander. Structural insights into interaction between mammalian methionine sulfoxide reductase B1 and thioredoxin.. Journal of Biomedicine and Biotechnology. (ISSN 1110-7243). 2012: 586539, 2012. 10.1155/2012/586539. 22505815.
Shumilina, Elena; Dobrovolska, Olena; Dikiy, Alexander. Evolution of Structural and Coordination Features within Methionine Sulfoxide Reductase B Family. .
Dobrovolska, Olena; Shumilina, Elena; Gladyshev, Vadim N; Dikiy, Alexander. Structural Analysis of Glutaredoxin Domain of Mus musculus Thioredoxin Glutathione Reductase.. PloS one. (ISSN 1932-6203). 7(12): e52914, 2012. 10.1371/journal.pone.0052914. 23300818.
Shumilinaa, Elena; Dobrovolska, Olena; Del Conteb, Rebecca; Holen, Henrik Waldal; Dikiya, Alexander. Competitive Zinc for Cobalt Substitution in Mammalian MsrB1 Overexpressed in E.coli : Structural and Functional Insights. .