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., ...Daha Fazla

FEBS LETTERS, cilt.516, ss.43-46, 2002 (SCI İndekslerine Giren Dergi) identifier identifier

Özet

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.