Premium
Docking studies reveal a selective binding of D ‐penicillamine to the transactivator protein of human immunodeficiency virus type 1
Author(s) -
Demirhan Ilhan,
Kanyalkar Meena,
Chandra Angelika,
Doerr Hans Wilhelm,
Coutinho Evans,
Loewer Johannes,
Saran Anil,
Chandra Prakash
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02468-7
Subject(s) - transactivation , penicillamine , chemistry , docking (animal) , van der waals force , binding site , cysteine , lead compound , biochemistry , stereochemistry , transcription factor , molecule , gene , enzyme , medicine , in vitro , nursing , organic chemistry
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.