Architecture of Succinate Dehydrogenase and Reactive Oxygen Species Generation

American Association for the Advancement of Science (AAAS) - Tập 299 Số 5607 - Trang 700-704 - 2003
Victoria Yankovskaya1, Rob Horsefield2, Susanna Törnroth‐Horsefield3, C. Luna-Chavez4,1, Hideto Miyoshi5, Christophe Léger6, Bernadette Byrne2, Gary Cecchini4,1, So Iwata3,2,7
1Molecular Biology Division, VA Medical Center, San Francisco, CA 94121, USA
2Department of Biological Sciences, Imperial College London, London SW7 2AY, UK.
3Department of Biochemistry, Uppsala University, BMC Box 576, S-75123 Uppsala, Sweden.
4Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA
5Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
6Inorganic Chemistry Laboratory, Oxford University, South Parks Road, Oxford OX1 3QR, UK
7Division of Biomedical Sciences Imperial College London, London SW7 2AZ, UK

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

For a review see

10.1016/S0005-2728(01)00238-9

For a review see

10.1016/S0005-2728(01)00228-6

10.1038/ng1095-144

10.1126/science.287.5454.848

10.1038/81551

10.1038/29331

10.1074/jbc.M104718200

10.1007/BF00245358

For a review see

10.1126/science.284.5422.1941

Guest J. R., J. Gen. Microbiol. 122, 171 (1981).

10.1128/JB.180.22.5989-5996.1998

10.1126/science.284.5422.1961

10.1038/46483

10.1016/S0005-2728(01)00237-7

10.1042/bj3040321

Materials and methods are available as supporting material on Science Online.

10.1107/S0108767390010224

10.1016/0003-9861(89)90561-4

10.1016/S0005-2728(97)00019-4

10.1016/0014-5793(92)80086-V

10.1007/PL00021452

10.1038/46972

10.1074/jbc.M011270200

10.1074/jbc.271.35.21020

10.1006/jmbi.2000.3509

10.1126/science.1068186

10.1086/321282

10.1136/jmg.39.9.617

10.1074/jbc.M204958200

10.1016/S0021-9258(19)75761-5

10.1074/jbc.274.37.26157

10.1073/pnas.72.8.2886

Supported by Biotechnology and Biological Sciences Research Council of the UK Structural Biology Network of Sweden Syngenta and the Department of Veterans Affairs and NIH grant GM61606. We thank E. Mitchell and A. Thompson at ESRF Grenoble and T. Tomizakiand C. Schulze-Briese at SLS for technical assistance. We also thank J. Abramson and T. Iverson for critically reading the manuscript. The coordinates for the native SQR and the DNP-17 complex are deposited with PDB (entries 1NEK and 1NEN respectively).