Insights into Function, Catalytic Mechanism, and Fold Evolution of Selenoprotein Methionine Sulfoxide Reductase B1 through Structural Analysis

Title
Insights into Function, Catalytic Mechanism, and Fold Evolution of Selenoprotein Methionine Sulfoxide Reductase B1 through Structural Analysis
Author(s)
김화영Aachmann FL[Aachmann FL]Sal LS[Sal LS]Marino SM[Marino SM]Gladyshev VN[Gladyshev VN]Dikiy A[Dikiy A]
Keywords
R-SULFOXIDE; NEISSERIA-MENINGITIDIS; BACKBONE DYNAMICS; CRYSTAL-STRUCTURE; CHEMICAL-SHIFT; PROTEIN; CYSTEINE; ZINC; SELENOCYSTEINE; THIOREDOXIN
Issue Date
201010
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.285, no.43, pp.33315 - 33323
Abstract
Methionine sulfoxide reductases protect cells by repairing oxidatively damaged methionine residues in proteins. Here, we report the first three-dimensional structure of the mammalian selenoprotein methionine sulfoxide reductase B1 (MsrB1), determined by high resolution NMR spectroscopy. Heteronuclear multidimensional spectra yielded NMR spectral assignments for the reduced form of MsrB1 in which catalytic selenocysteine (Sec) was replaced with cysteine (Cys). MsrB1 consists of a central structured core of two beta-sheets and a highly flexible, disordered N-terminal region. Analysis of pH dependence of NMR signals of catalytically relevant residues, comparison with the data for bacterial MsrBs, and NMR-based structural analysis of methionine sulfoxide (substrate) and methionine sulfone (inhibitor) binding to MsrB1 at the atomic level reveal a mechanism involving catalytic Sec(95) and resolving Cys(4) residues in catalysis. The MsrB1 structure differs from the structures of Cys-containing MsrBs in the use of distal selenenylsulfide, residues needed for catalysis, and the mode in which the active form of the enzyme is regenerated. In addition, this is the first structure of a eukaryotic zinc-containing MsrB, which highlights the structural role of this metal ion bound to four conserved Cys. We integrated this information into a structural model of evolution of MsrB superfamily.
URI
http://hdl.handle.net/YU.REPOSITORY/23491http://dx.doi.org/10.1074/jbc.M110.132308
ISSN
0021-9258
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의과대학 > 생화학.분자생물학교실 > Articles
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