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Characteristics of a 50S ribosomal subunit precursor particle as a substrate for ermE methyltransferase activity and erythromycin binding in Staphylococcus aureus.
Pokkunuri, Indira; Champney, W Scott.
Afiliación
  • Pokkunuri I; Department of Biochemistry and Molecular Biology, J.H. Quillen College Medicine, East Tennessee State University, Johnson City, Tennessee 37614, USA.
RNA Biol ; 4(3): 147-53, 2007 Nov.
Article en En | MEDLINE | ID: mdl-18094627
Erythromycin is a macrolide antibiotic that inhibits not only mRNA translation but also 50S ribosomal subunit assembly in bacterial cells. An important mechanism of erythromycin resistance is the methylation of 23S rRNA by erm methyl transferase enzymes. A model for 50S ribosomal subunit formation suggests that the precursor particle which accumulates in erythromycin treated cells is the target for methyl transferase activity. Hybridization experiments identified the presence of 23S rRNA in the 50S precursor particle. The protein content of the 50S precursor particle was analyzed by MALDI-TOF mass spectrophotometry. These studies have identified 23 of 36 50S ribosomal proteins in the precursor. Methyltransferase assays demonstrated that the 50S precursor particle was a substrate for ermE methyltransferase. Competition experiments indicated that the enzyme could displace erythromycin from the 50S precursor particle and that the methyltransferase had a higher association constant for the precursor particle compared to that of erythromycin. Inhibition experiments showed that macrolide, lincosamide and streptogramin B compounds bound to the precursor particle with similar affinity and inhibited the ermE methyltransferase activity. These studies shed light on the interaction of ermE methyltransferase and erythromycin in this clinically important pathogen.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Staphylococcus aureus / ARN Ribosómico / Eritromicina / Subunidades Ribosómicas Grandes Bacterianas / Metiltransferasas / Antibacterianos Tipo de estudio: Prognostic_studies Idioma: En Revista: RNA Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Staphylococcus aureus / ARN Ribosómico / Eritromicina / Subunidades Ribosómicas Grandes Bacterianas / Metiltransferasas / Antibacterianos Tipo de estudio: Prognostic_studies Idioma: En Revista: RNA Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos