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Science 31 January 2003:
Vol. 299. no. 5607, pp. 700 - 704
DOI: 10.1126/science.1079605
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Reports

Architecture of Succinate Dehydrogenase and Reactive Oxygen Species Generation

Victoria Yankovskaya,1* Rob Horsefield,2* Susanna Törnroth,3* César Luna-Chavez,14dagger Hideto Miyoshi,5 Christophe Léger,6ddagger Bernadette Byrne,2 Gary Cecchini,14§ So Iwata237§

The structure of Escherichia coli succinate dehydrogenase (SQR), analogous to the mitochondrial respiratory complex II, has been determined, revealing the electron transport pathway from the electron donor, succinate, to the terminal electron acceptor, ubiquinone. It was found that the SQR redox centers are arranged in a manner that aids the prevention of reactive oxygen species (ROS) formation at the flavin adenine dinucleotide. This is likely to be the main reason SQR is expressed during aerobic respiration rather than the related enzyme fumarate reductase, which produces high levels of ROS. Furthermore, symptoms of genetic disorders associated with mitochondrial SQR mutations may be a result of ROS formation resulting from impaired electron transport in the enzyme.

1 Molecular Biology Division, VA Medical Center, San Francisco, CA 94121, USA.
2 Department of Biological Sciences, Imperial College London, London SW7 2AY, UK.
3 Department of Biochemistry, Uppsala University, BMC Box 576, S-75123 Uppsala, Sweden.
4 Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.
5 Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
6 Inorganic Chemistry Laboratory, Oxford University, South Parks Road, Oxford OX1 3QR, UK.
7 Division of Biomedical Sciences, Imperial College London, London SW7 2AZ, UK.
*   These authors contributed equally to this work.

dagger    Present address: Center for Biophysics and Computational Biology, Department of Biophysics, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.

ddagger    Present address: BIP07-CNRS, 31, Chemin Joseph Aiguier, 13402 Marseille, France.

§   To whom correspondence should be addressed. E-mail: s.iwata{at}ic.ac.uk or ceccini{at}itsa.ucsf.edu

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