title: Structural plasticity of the thioredoxin recognition site of yeast methionine S-sulfoxide reductase Mxr1.
abstract: The methionine S-sulfoxide reductase MsrA catalyzes the reduction of methionine sulfoxide, a ubiquitous reaction depending on the thioredoxin system. To investigate interactions between MsrA and thioredoxin (Trx), we determined the crystal structures of yeast MsrA/Mxr1 in their reduced, oxidized, and Trx2-complexed forms, at 2.03, 1.90, and 2.70 Å, respectively. Comparative structure analysis revealed significant conformational changes of the three loops, which form a plastic "cushion" to harbor the electron donor Trx2. The flexible C-terminal loop enabled Mxr1 to access the methionine sulfoxide on various protein substrates. Moreover, the plasticity of the Trx binding site on Mxr1 provides structural insights into the recognition of diverse substrates by a universal catalytic motif of Trx.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Ma
authors.forename: Peng-Chao
authors.initials: PC
authors.lastname: Guo
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Shi
authors.forename: Ming
authors.initials: M
authors.lastname: Luo
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Tan
authors.forename: Yuxing
authors.initials: Y
authors.lastname: Chen
authors.forename: Cong-Zhao
authors.initials: CZ
authors.lastname: Zhou
mesh_terms: D020816:Amino Acid Motifs; D008715:Methionine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D051150:Methionine Sulfoxide Reductases / Q000737:chemistry* / Q000378:metabolism; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D020836:Protein Structure, Quaternary; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013879:Thioredoxins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C516110:TRX2 protein, S cerevisiae; D013879:Thioredoxins; D008715:Methionine; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C487504:MsrA protein, S cerevisiae; C013111:methionine sulfoxide