Structural basis for selectivity and toxicity of ribosomal antibiotics.
Ribosomal antibiotics must discriminate between bacterial and eukaryotic ribosomes to various extents. Despite major differences in bacterial and eukaryotic ribosome structure, a single nucleotide or amino acid determines the selectivity of drugs affecting protein synthesis. Analysis of resistance mutations in bacteria allows the prediction of whether cytoplasmic or mitochondrial ribosomes in eukaryotic cells will be sensitive to the drug. This has important implications for drug specificity and toxicity. Together with recent data on the structure of ribosomal subunits these data provide the basis for development of new ribosomal antibiotics by rationale drug design.
Böttger
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EC
Institut für Medizinische Mikrobiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. boettger@immv.unizh.ch
Springer
B
B
Prammananan
T
T
Kidan
Y
Y
Sander
P
P
D000483:Alleles; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D003593:Cytoplasm / Q000378:metabolism; D016208:Databases, Factual; D015195:Drug Design; D008034:Lincomycin / Q000737:chemistry; D018942:Macrolides; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D020102:Mycobacterium smegmatis / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013997:Time Factors; D014769:Virginiamycin / Q000737:chemistry
D000900:Anti-Bacterial Agents; D018942:Macrolides; D012336:RNA, Ribosomal, 16S; D014769:Virginiamycin; D008034:Lincomycin