Docking studies reveal a selective binding Of D-penicillamine to the transactivator protein of human immunodeficiency virus type 1

DEMİRHAN I., Kanyalkar M., Chandra A., Doerr H., Coutinho E., Loewer J., ...More

FEBS LETTERS, vol.516, pp.43-46, 2002 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 516
  • Publication Date: 2002
  • Doi Number: 10.1016/s0014-5793(02)02468-7
  • Journal Name: FEBS LETTERS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.43-46
  • Erciyes University Affiliated: No

Abstract

DOCK and Affinity, studies were carried out to study the binding Of D- and L-penicillamine to the transactivator protein (tat) of human immunodeficiency virus type 1 (HIV-1). These studies reveal a selective binding 4 D-penicillamine to the cysteine-rich region covering amino acid residues 20-38 of the tat protein. A careful analysis of the components of the binding energy of the D- and L-isomers reveals that the D-isomer has a more favorable van der Waals interaction resulting from an optimal placement of the dimethylthiomethyl side chain in the binding site. This observation matches the experimental data that D-penicillamine is a more potent inhibitor of tat-mediated transactivation than the L-isomer. The docking and experimental data offer an interesting approach to design structural molecules with potential application to block signal functions of the tat protein in HIV-1 pathogenesis. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.