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Structure of an inhibitor complex of the proteinase from feline immunodeficiency virus

Nature Structural Biology volume 2, pages 480–488 (1995) Cite this article

Abstract

The crystal structure of a recombinant form of the proteinase encoded by the feline immunodeficiency virus (FIV PR) has been solved at 2 Å resolution and refined to an R-factor of 0.148. The refined structure includes a peptidomimetic, statine-based inhibitor, LP-149, which is an even more potent inhibitor of HIV PR. Kinetic parameters were obtained for the cleavage of five substrates by FIV PR, and inhibition constants were measured for four inhibitors. The structure of FIV PR resembles other related retroviral enzymes although few inhibitors of HIV PR are capable of inhibiting FIV PR. The structure of FIV PR will enhance our knowledge of this class of enzymes, and will direct testing of new proteinase inhibitors in a feline animal model.

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Authors and Affiliations

  1. Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Frederick, Maryland, 21702, USA

    Alexander Wlodawer, Alla Gustchina, Ludmila Reshetnikova, Jacek Lubkowski & Alexander Zdanov

  2. Engelhardt Institute of Molecular Biology, Russian Academy of Science, Moscow, 117984, Russia

    Ludmila Reshetnikova

  3. Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana, 46285, USA

    Kwan Y. Hui & Eddie L. Angleton

  4. Department of Biochemistry and Molecular Biology, University of Florida, Box 100245, Gainesville, Florida, 32610, USA

    William G. Farmerie, Deepa Bhatt, Li Zhang & Ben M. Dunn

  5. Department of Pathology and Experimental Medicine, University of Florida, Box 100275, Gainesville, Florida, 32610, USA

    Maureen M. Goodenow

Authors
  1. Alexander Wlodawer
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  2. Alla Gustchina
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  3. Ludmila Reshetnikova
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  4. Jacek Lubkowski
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  5. Alexander Zdanov
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  6. Kwan Y. Hui
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  7. Eddie L. Angleton
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  8. William G. Farmerie
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  9. Maureen M. Goodenow
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  10. Deepa Bhatt
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  11. Li Zhang
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  12. Ben M. Dunn
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Wlodawer, A., Gustchina, A., Reshetnikova, L. et al. Structure of an inhibitor complex of the proteinase from feline immunodeficiency virus. Nat Struct Mol Biol 2, 480–488 (1995). https://doi.org/10.1038/nsb0695-480

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