A molecular modeling study of antibiotics–RNA interactions: application to HIV-1 Rev response element
| Autor: | Shu-Yun Le, Jacob V Maizel, V Pramodh, N Pattabiraman |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Molecular model
Base pair viruses Molecular Modeling Site Peptide Biochemistry Messenger-Rna Base-Pairs Antibiotics-Rna Interaction Virus Type-Iii Physical and Theoretical Chemistry Binding site chemistry.chemical_classification Hiv-1 Rev Response Element Chemistry Protein Aminoglycoside RNA Condensed Matter Physics Footprinting Recognition Binding-Element Pharmacophore Force-Field |
| Zdroj: | Journal of Molecular Structure: THEOCHEM. 423:125-136 |
| ISSN: | 0166-1280 |
| Popis: | HIV-1 Rev protein interaction with the Response Element (RRE) RNA is important for the regulation and gene expression in HIV-1. Molecules that inhibit this interaction are potential anti-HIV drugs. Some aminoglycoside antibiotics, such as neomycin B and tobramycin, have been found to inhibit the binding of Rev to RRE by specifically binding to the high-affinity binding site of RRE. In this paper, we present a three-dimensional model for these antibiotics–RRE complexes. From our modeling studies, we found these antibiotics to have restricted conformations both in the bound and unbound state. In the restricted conformations four of the amino groups point to one side of the antibiotic molecule such that they can form salt bridges with the phosphate groups of U45, G47 and G48 in the case of tobramycin and with the phosphate groups of A44, G47 and G48 in the case of neomycin B. In addition, some of the amino and hydroxyl groups in the antibiotics interact favorably with N7 and/or O6 atoms of GGG (nt 46–48). In the antibiotics–RNA complexes, the two non-Watson–Crick base pairs are formed as observed in the case of Rev and the 17mer peptide from Rev when bound to RRE. These models are consistent with the known footprinting data and also the inhibitory data for these antibiotics against the binding of Rev to RRE. These models could be used to develop a pharmacophore to search for compounds in the chemical databases that can inhibit the binding of Rev to RRE. |
| Databáze: | OpenAIRE |
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