title: Docking studies reveal a selective binding of D-penicillamine to the transactivator protein of human immunodeficiency virus type 1.
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.
authors.affiliation: Institute of Medical Virology, Frankfurt University Medical School, 60590, Frankfurt, Germany.
authors.forename: Ilhan
authors.initials: I
authors.lastname: Demirhan
authors.forename: Meena
authors.initials: M
authors.lastname: Kanyalkar
authors.forename: Angelika
authors.initials: A
authors.lastname: Chandra
authors.forename: Hans Wilhelm
authors.initials: HW
authors.lastname: Doerr
authors.forename: Evans
authors.initials: E
authors.lastname: Coutinho
authors.forename: Johannes
authors.initials: J
authors.lastname: Loewer
authors.forename: Anil
authors.initials: A
authors.lastname: Saran
authors.forename: Prakash
authors.initials: P
authors.lastname: Chandra
mesh_terms: D001665:Binding Sites; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003198:Computer Simulation; D015696:Gene Products, tat / Q000737:chemistry* / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D008958:Models, Molecular; D010396:Penicillamine / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D013237:Stereoisomerism; D013816:Thermodynamics; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus; D015500:Chloramphenicol O-Acetyltransferase; D010396:Penicillamine