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Determination of structurally conservative amino acids of the HIV-1 protein gp120 V3 loop as promising targets for drug design by protein engineering approaches

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Abstract

Based on the published NMR spectroscopy data, three-dimensional structures of the HIV-1 gp120 protein V3 loop were obtained by computer modeling in the viral strains HIV-Haiti and HIV-MN. In both cases, the secondary structure elements and conformations of irregular stretches were determined for the fragment representing the principal antigenic determinant of the virus, as well as determinants of the cellular tropism and syncytium formation. Notwithstanding the high variability of the amino acid sequence of gp120 protein, more than 50% of the V3 loop residues retained their conformations in the different HIV-1 virions. The combined analysis of the findings and the literature data on the biological activity of the individual residues of the HIV-1 V3 loop resulted in identification of its structurally conservative amino acids, which seem to be promising targets for antiviral drug design by protein engineering approaches.

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Abbreviations

HIV-1:

human immunodeficiency virus type 1

PND:

principal neutralizing determinant

IDE:

immunodominant epitope

TFE:

trifluoroethanol

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Authors and Affiliations

  1. Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, ul. Kuprevicha 5/2, 220141, Minsk, Belarus

    A. M. Andrianov

  2. Institute of Biophysics and Cell Engineering, National Academy of Sciences of Belarus, ul. Akademicheskaya 27, 220072, Minsk, Belarus

    V. G. Veresov

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Correspondence to A. M. Andrianov.

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Original Russian Text © A. M. Andrianov, V. G. Veresov, 2006, published in Biokhimiya, 2006, Vol. 71, No. 8, pp. 1119–1128.

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Andrianov, A.M., Veresov, V.G. Determination of structurally conservative amino acids of the HIV-1 protein gp120 V3 loop as promising targets for drug design by protein engineering approaches. Biochemistry (Moscow) 71, 906–914 (2006). https://doi.org/10.1134/S000629790608013X

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  • DOI: https://doi.org/10.1134/S000629790608013X

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