Structural insights into the cofactor-assisted substrate recognition of yeast quinone oxidoreductase Zta1 |
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Authors: | Guo Peng-Chao Ma Xiao-Xiao Bao Zhang-Zhi Ma Jin-Di Chen Yuxing Zhou Cong-Zhao |
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Institution: | Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei Anhui 230027, People’s Republic of China |
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Abstract: | Quinone oxidoreductase (QOR EC1.6.5.5) catalyzes the reduction of quinone to hydroxyquinone using NADPH as a cofactor. Here we present the crystal structure of the ζ-crystallin-like QOR Zta1 from Saccharomycescerevisiae in apo-form at 2.00 Å and complexed with NADPH at 1.59 Å resolution. Zta1 forms a homodimer, with each subunit containing a catalytic and a cofactor-binding domain. Upon NADPH binding to the interdomain cleft, the two domains shift towards each other, producing a better fit for NADPH, and tightening substrate binding. Computational simulation combined with site-directed mutagenesis and enzymatic activity analysis defined a potential quinone-binding site that determines the stringent substrate specificity. Moreover, multiple-sequence alignment and kinetics assays implied that a single-residue change from Arg in lower organisms to Gly in vertebrates possibly resulted in elevation of enzymatic activity of ζ-crystallin-like QORs throughout evolution. |
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Keywords: | Abbreviations: QOR quinone oxidoreductase NQ 1 2-naphthoquinone PQ 9 10-phenanthrenequinone |
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