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

Ilhan Demirhan, Meena Kanyalkar, Angelika Chandra, Hans Wilhelm Doerr, Evans Coutinho, Johannes Loewer, Anil Saran, Prakash Chandra

Journal: FEBS letters 2002;516(1-3):43-6

PMID: 11959100

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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 of 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.

Address: Institute of Medical Virology, Frankfurt University Medical School, 60590, Frankfurt, Germany.

DOI: 10.1016/s0014-5793(02)02468-7

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MeSH Terms: Binding Sites, Chloramphenicol O-Acetyltransferase, Computer Simulation, Gene Products, tat, HIV Long Terminal Repeat, HIV-1, Humans, In Vitro Techniques, Jurkat Cells, Models, Molecular, Penicillamine, Protein Binding, Stereoisomerism, Thermodynamics, Transcriptional Activation, Transfection, tat Gene Products, Human Immunodeficiency Virus