Which aminoglycoside ring is most important for binding? a hydropathic analysis of gentamicin, paromomycin, and analogues
| Autor: | Jason P. Rife, Derek J. Cashman, Glen E. Kellogg |
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| Rok vydání: | 2001 |
| Předmět: |
Models
Molecular Molecular model Paromomycin Stereochemistry Molecular Sequence Data Clinical Biochemistry Pharmaceutical Science Biochemistry Structure-Activity Relationship chemistry.chemical_compound RNA Ribosomal 16S Drug Discovery Carbohydrate Conformation Escherichia coli medicine Nuclear Magnetic Resonance Biomolecular Molecular Biology Ribosomal DNA Antibacterial agent Binding Sites Chemistry Organic Chemistry Aminoglycoside RNA Ribosomal RNA Anti-Bacterial Agents Aminocyclitol Aminoglycosides Carbohydrate Sequence Thermodynamics Molecular Medicine Gentamicins Algorithms medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 11:119-122 |
| ISSN: | 0960-894X |
| Popis: | The NMR structures of gentamicin and paromomycin in complex with the A-site of Escherichia coli 16S ribosomal RNA were modified with molecular modeling to 12 analogues. The intermolecular interactions between these molecules and RNA were examined using the HINT (Hydropathic INTeractions) computational model to obtain interaction scores that have been shown previously to be related to free energy. The calculations correlated well with experimental binding data, and the interaction scores were used to analyze the specific structural features of each aminoglycoside that contribute to the overall binding with the 16S rRNA. Our calculations indicate that, while ring I binds to the main binding pocket of the rRNA A-site, ring IV of paromomycin-based aminoglycosides contributes significantly to the overall binding. |
| Databáze: | OpenAIRE |
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