title: Binding of aminoglycosidic antibiotics to the oligonucleotide A-site model and 30S ribosomal subunit: Poisson-Boltzmann model, thermal denaturation, and fluorescence studies.
abstract: The binding of paromomycin and similar antibiotics to the oligonucleotide A-site model and the small (30S) ribosomal subunit has been studied using continuum electrostatics methods. Crystallographic information from complexes of paromomycin, tobramycin, and Geneticin bound to an A-site oligonucleotide, and paromomycin and streptomycin complexed to the 30S subunit was used as a foundation to develop structures of similar antibiotics in the same ribosomal binding site. Relative binding free energies were calculated by combining the electrostatic contribution, which was obtained by solving the Poisson-Boltzmann equation, with a surface-area-dependent apolar term and contributions from conformational changes. These computed results showed good correlation with the experimental data resulting from fluorescence binding assays and thermal denaturation studies, demonstrating the ability of the Poisson-Boltzmann model to provide insight into the electrostatic mechanisms for aminoglycoside binding and direction for designing more effective antibiotics.
authors.affiliation: Department of Chemistry and Biochemistry, University of California-San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Yang
authors.forename: Joanna
authors.initials: J
authors.lastname: Trylska
authors.forename: Yitzhak
authors.initials: Y
authors.lastname: Tor
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001665:Binding Sites; D005453:Fluorescence; D009691:Nucleic Acid Denaturation; D009841:Oligonucleotides / Q000737:chemistry*; D012336:RNA, Ribosomal, 16S / Q000737:chemistry*; D012270:Ribosomes / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D009841:Oligonucleotides; D012336:RNA, Ribosomal, 16S