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

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...

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Bibliographic Details
Published in:FEBS letters 2002-04, Vol.516 (1), p.43-46
Main Authors: Demirhan, Ilhan, Kanyalkar, Meena, Chandra, Angelika, Doerr, Hans Wilhelm, Coutinho, Evans, Loewer, Johannes, Saran, Anil, Chandra, Prakash
Format: Article
Language:English
Subjects:
Binding Sites
Chloramphenicol O-Acetyltransferase - genetics
Computer Simulation
D-Penicillamine
Docking
Gene Products, tat - chemistry
Gene Products, tat - metabolism
HIV Long Terminal Repeat
HIV-1 - drug effects
HIV-1 - genetics
HIV-1 - metabolism
Human immunodeficiency virus type 1 transactivation
Humans
In Vitro Techniques
Jurkat Cells
Models, Molecular
Penicillamine - chemistry
Penicillamine - metabolism
Penicillamine - pharmacology
Protein Binding
Stereoisomerism
tat Gene Products, Human Immunodeficiency Virus
tat protein
Thermodynamics
Transcriptional Activation - drug effects
Transfection
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Summary: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.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(02)02468-7