title: Structural insights into interaction between mammalian methionine sulfoxide reductase B1 and thioredoxin.
abstract: Maintenance of the cellular redox balance has vital importance for correcting organism functioning. Methionine sulfoxide reductases (Msrs) are among the key members of the cellular antioxidant defence system. To work properly, methionine sulfoxide reductases need to be reduced by their biological partner, thioredoxin (Trx). This process, according to the available kinetic data, represents the slowest step in the Msrs catalytic cycle. In the present paper, we investigated structural aspects of the intermolecular complex formation between mammalian MsrB1 and Trx. NMR spectroscopy and biocomputing were the two mostly used through the research approaches. The formation of NMR detectable MsrB1/Trx complex was monitored and studied in attempt to understand MsrB1 reduction mechanism. Using NMR data, molecular mechanics, protein docking, and molecular dynamics simulations, it was found that intermediate MsrB1/Trx complex is stabilized by interprotein β-layer. The complex formation accompanied by distortion of disulfide bond within MsrB1 facilitates the reduction of oxidized MsrB1 as it is evidenced by the obtained data.
authors.affiliation: Department of Biotechnology, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Olena
authors.initials: O
authors.lastname: Dobrovolska
authors.forename: Georgy
authors.initials: G
authors.lastname: Rychkov
authors.forename: Elena
authors.initials: E
authors.lastname: Shumilina
authors.forename: Kirill
authors.initials: K
authors.lastname: Nerinovski
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmidt
authors.forename: Konstantin
authors.initials: K
authors.lastname: Shabalin
authors.forename: Alexander
authors.initials: A
authors.lastname: Yakimov
authors.forename: Alexander
authors.initials: A
authors.lastname: Dikiy
mesh_terms: D000818:Animals; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D051150:Methionine Sulfoxide Reductases / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D011485:Protein Binding; D013879:Thioredoxins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D004220:Disulfides; D013879:Thioredoxins; D051150:Methionine Sulfoxide Reductases