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Functional analysis of yeast fRMsr and its role in the reduction of free methionine‐R‐sulfoxides in yeast and mammalian cells
Author(s) -
Lee Byung Cheon,
Marino Stefano M,
Le Dung Tien,
Zhang Yan,
Gladyshev Vadim N
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.861.3
Subject(s) - msra , methionine sulfoxide reductase , biochemistry , yeast , saccharomyces cerevisiae , methionine , escherichia coli , enzyme , chemistry , methionine sulfoxide , cysteine , thioredoxin , biology , gene , amino acid
Methionine sulfoxide reductases (Msrs) are oxidoreductases that catalyze thiol‐dependent reduction of oxidized methionines. MsrA and MsrB are well known Msr enzymes, which have reduce methionine‐S‐sulfoxide (Met‐S‐SO) and methionine‐R‐sulfoxide (Met‐R‐SO), respectively. Recently, an additional Msr specific for free Met‐R‐SO from an Escherichia coli was discovered. Here, we characterized occurrence and function of fRMsr homologs via comparative genomics and experimental analyses in Saccharomyces cerevisiae . We also propose a reaction mechanism of this enzyme based on an enzyme‐substrate docking model using computational molecular dynamics and on the experiments involving trapping fRMsr‐based intermolecular intermediates with thioredoxin 1. In addition, transfection of fRMsr into mammalian SK‐Hep1 cells increased oxidative stress resistance and restored deficiency of these cells in the reduction of free Met‐R‐SO. Altogether, the data shows yeast fRMsr is the major protein that reduces free Met‐R‐SO in yeast cells and can also support this function in mammalian cells.