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Resistance mutations reveal the atovaquone-binding domain of cytochrome b in malaria parasites

  1. Indresh K. Srivastava1,†,
  2. Joanne M. Morrisey1,
  3. Elisabeth Darrouzet2,
  4. Fevzi Daldal2,
  5. Akhil B. Vaidya1

Article first published online: 1 MAR 2002

DOI: 10.1046/j.1365-2958.1999.01515.x

Issue

Molecular Microbiology

Molecular Microbiology

Volume 33, Issue 4, pages 704–711, August 1999

Additional Information

How to Cite

Srivastava, I. K., Morrisey, J. M., Darrouzet, E., Daldal, F. and Vaidya, A. B. (1999), Resistance mutations reveal the atovaquone-binding domain of cytochrome b in malaria parasites. Molecular Microbiology, 33: 704–711. doi: 10.1046/j.1365-2958.1999.01515.x

Author Information

  1. 1

    Department of Microbiology and Immunology, 2900 Queen Lane, MCP Hahnemann School of Medicine, Philadelphia, PA 19129, USA.,

  2. 2

    Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.

*Akhil B. Vaidya. E-mail vaidyaa@mcphu.edu; Tel. (+1) 215 991 8557; Fax (+1) 215 843 4152.

Publication History

  1. Issue published online: 1 MAR 2002
  2. Article first published online: 1 MAR 2002

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References

  • 1
    Brasseur, G., Saribas, A.S., Daldal, F. (1996) A compilation of mutations located in the cytochrome b subunit of the bacterial and mitochondrial bc1 complex. Biochim Biophys Acta 1275: 61–69.
  • 2
    Canfield, C.J., Pudney, M., Gutteridge, W.E. (1995) Interactions of atovaquone with other antimalarial drugs against Plasmodium falciparum in vitro. Exp Parasitol 80: 373–381.
  • 3
    Chiodini, P.L., Conlon, C.P., Hutchinson, D.B., Farquhar, J.A., Hall, A.P., Peto, T.E., et al (1995) Evaluation of atovaquone in the treatment of patients with uncomplicated Plasmodium falciparum malaria. J Antimicrob Chemother 36: 1073–1078.
  • 4
    Feagin, J.E. (1994) The extrachromosomal DNAs of apicomplexan parasites. Annu Rev Microbiol 48: 81–104.
  • 5
    Fieser, L.F., Berliner, E., Bondhus, F.J., Chang, F.C., Dauben, W.G., Etlinger, M.G., et al (1948) Naphthoquinone antimalarials. I–XVII. J Am Chem Soc 70: 3151–3244.
  • 6
    Friedberg, E.C., Walker, J.C., Siede, W. (1995) DNA Repair and Mutagenesis. Washington, DC: American Society for Microbiology Press.
  • 7
    Fry, M. & Pudney, M. (1992) Site of action of the antimalarial hydroxynaphthoquinone, 2-[trans-4-(4′-chlorophenyl) cyclohexyl]-3-hydroxy1,4naphthoquinone (566C80). Biochem Pharmacol 43: 1545–1553.
  • 8
    Hudson, A.T., Dickens, M., Ginger, C.D., Gutteridge, W.E., Holdich, T., Hutchinson, D.B.A., et al (1991) 566C80: a broad spectrum anti-infective agent with activity against malaria and opportunistic infections in IDS patients. Drugs Exp Clin Res 17: 427–435.
  • 9
    Hughes, W., Leoung, G., Kramer, F., Bozzette, S.A., Safrin, S., Frame, P., et al (1993) Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS. N Engl J Med 328: 1521–1527.
  • 10
    Iwata, S., Lee, J.W., Okada, K., Lee, J.K., Iwata, M., Rasmussen, B., et al (1998) Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex. Science 281: 64–71.
  • 11
    Kim, H., Xia, D., Yu, C.A., Xia, J.Z., Kachurin, A.M., Zhang, L., et al (1998) Inhibitor binding changes domain mobility in the iron-sulfur protein of the mitochondrial bc1 complex from bovine heart. Proc Natl Acad Sci USA 95: 8026–8033.
  • 12
    Kovacs, J.A. (1992) Efficacy of atovaquone in treatment of toxoplasmosis in patients with AIDS. The NIAID-Clinical Center Intramural AIDS Program. Lancet 340: 637–638.
  • 13
    Looareesuwan, S., Viravan, C., Webster, H.K., Kyle, D.E., Hutchinson, D.B., Canfield, C.J. (1996) Clinical studies of atovaquone, alone or in combination with other antimalarial drugs, for treatment of acute uncomplicated malaria in Thailand. Am J Trop Med Hyg 54: 62–66.
  • 14
    McIntosh, M.T., Srivastava, R., Vaidya, A.B. (1998) Divergent evolutionary constraints on mitochondrial and nuclear genomes of malaria parasites. Mol Biochem Parasitol 95: 69–80.
  • 15
    Preiser, P.R., Wilson, R.J.M., Moore, P.W., McCready, S., Hajibhageri, M.A.N., Blight, K.J., et al (1996) Recombination associated with the replication of malarial mitochondrial DNA. EMBO J 15: 684–693.
  • 16
    Scheibel, L.W. (1988) Plasmodial metabolism and related organellar function during various stages of the life-cycle: carbohydrates. In Malaria: Principles and Practice of Malariology, Vol. 1. Wernsdorfer, W.H., and McGregor, I. (eds). New York: Churchill Livingstone, pp. 171–217.
  • 17
    Srivastava, I.K. & Vaidya, A.B. (1999) A mechanism for the synergistic antimalarial action of atovaquone and proguanil. Antimicrob Agents Chemother 43: 1334–1339.
  • 18
    Srivastava, I.K.H., Rottenberg, Vaidya, A.B. (1997) Atovaquone, a broad spectrum antiparasitic drug, collapses mitochondrial membrane potential in a malarial parasite. J Biol Chem 272: 3961–3966.
  • 19
    Trumpower, B.L. & Gennis, R.B. (1994) Energy transduction by cytochrome complexes in mitochondrial and bacterial respiration: the enzymology of coupling electron transfer reactions to transmembrane proton translocation. Annu Rev Biochem 63: 675–716.
  • 20
    Vaidya, A.B. (1998) Mitochondrial physiology as a target for atovaquone and other antimalarials. In Malaria: Parasite Biology, Pathogenesis, and Protection. Sherman, I.W. (ed.). Washington, DC: American Society for Microbiology Press, pp. 355–368.
  • 21
    Vaidya, A.B. & Arasu, P. (1987) Tandemly arranged gene clusters of malarial parasites that are highly conserved and transcribed. Mol Biochem Parasitol 22: 249–257.
  • 22
    Vaidya, A.B., Akella, R., Suplick, K. (1989) Sequences similar to genes for two mitochondrial proteins and portions of ribosomal RNA in tandemly arrayed 6 kilobase pair DNA of a malarial parasite. Mol Biochem Parasitol 35: 97–107.
  • 23
    Vaidya, A.B., Lashgari, M.S., Pologe, L.G., Morrisey, J. (1993 a) Structural features of Plasmodium cytochrome b that may underlie susceptibility to 8-aminoquinolines and hydroxnaphthoquinones. Mol Biochem Parasitol 58: 33–42.
  • 24
    Vaidya, A.B., Morrisey, J., Plowe, C.V., Kaslow, D.C., Wellems, T.E. (1993 b) Unidirectional dominance of cytoplasmic inheritance in two genetic crosses of Plasmodium falciparum. Mol Cell Biol 13: 7349–7357.
  • 25
    Xia, D., Yu, C.A., Kim, H., Xia, J.Z., Kachurin, A.M., Zhang, L., et al (1997) Crystal structure of the cytochrome bc1 complex from bovine heart mitochondria. Science 277: 60–66.
  • 26
    Zhang, Z., Huang, L., Shulmeister, V.M., Chi, Y.I., Kim, K.K., Hung, L.W., et al (1998) Electron transfer by domain movement in cytochrome bc1. Nature 392: 677–684.
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