Crystal Structure of a New Type of NADPH-Dependent Quinone Oxidoreductase (QOR2) from Escherichia coli

Laboratory of Biophysics, School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul 151-742, Republic of Korea.
Journal of Molecular Biology (Impact Factor: 4.33). 06/2008; 379(2):372-84. DOI: 10.1016/j.jmb.2008.04.003
Source: PubMed


Escherichia coli QOR2 [NAD(P)H-dependent quinone oxidoreductase; a ytfG gene product], which catalyzes two-electron reduction of methyl-1,4-benzoquinone, is a new type of quinone-reducing enzyme with distinct primary sequence and oligomeric conformation from previously known quinone oxidoreductases. The crystal structures of native QOR2 and the QOR2-NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) complex reveal that QOR2 consists of two domains (N-domain and C-domain) resembling those of NmrA, a negative transcriptional regulator that belongs to the short-chain dehydrogenase/reductase family. The N-domain, which adopts the Rossmann fold, provides a platform for NADPH binding, whereas the C-domain, which contains a hydrophobic pocket connected to the NADPH-binding site, appears to play important roles in substrate binding. Asn143 near the NADPH-binding site has been identified to be involved in substrate binding and catalysis from structural and mutational analyses. Moreover, compared with wild-type strain, the qor2-overexpressing strain shows growth retardation and remarkable decrease in several enzymes involved in carbon metabolism, suggesting that QOR2 could play some physiological roles in addition to quinone reduction.

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    • "Escherichia coli possesses several NADH/NADPHdependent quinone oxidoreductases (Fig. 1), including tryptophan repressor-binding protein WrbA, modulator of drug activity (MdaB), quinone oxidoreductase QoR, chromate reductase YieF and quinone oxidoreductase YtfG (Thorn et al., 1995; Ackerley et al., 2004; Adams and Jia, 2005; Patridge and Ferry, 2006; Kim et al., 2008). They share a structural similarity, each containing a flavin cofactor at the active site, with broad substrate specificities . "
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