Acquired ribosomal RNA (rRNA) methylation has emerged as a significant mechanism of aminoglycoside resistance in pathogenic bacterial infections. Modification of a single nucleotide in the ribosome decoding center by the aminoglycoside-resistance 16S rRNA (mG1405) methyltransferases effectively blocks the action of all 4,6-deoxystreptamine ring-containing aminoglycosides, including the latest generation of drugs. To define the molecular basis of 30S subunit recognition and G1405 modification by these enzymes, we used a -adenosyl-L-methionine analog to trap the complex in a postcatalytic state to enable determination of a global 3.
View Article and Find Full Text PDFAcquired ribosomal RNA (rRNA) methylation has emerged as a significant mechanism of aminoglycoside resistance in pathogenic bacterial infections. Modification of a single nucleotide in the ribosome decoding center by the aminoglycoside-resistance 16S rRNA (m G1405) methyltransferases effectively blocks the action of all 4,6-deoxystreptamine ring-containing aminoglycosides, including the latest generation of drugs. To define the molecular basis of 30S subunit recognition and G1405 modification by these enzymes, we used a S-adenosyl-L-methionine (SAM) analog to trap the complex in a post-catalytic state to enable determination of an overall 3.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
April 2022
Changes in bacterial ribosomal RNA (rRNA) methylation status can alter the activity of diverse groups of ribosome-targeting antibiotics. These modifications are typically incorporated by a single methyltransferase that acts on one nucleotide target and rRNA methylation directly prevents drug binding, thereby conferring drug resistance. Loss of intrinsic methylation can also result in antibiotic resistance.
View Article and Find Full Text PDFGeorgian Med News
September 2020
Generalized parodontal diseases (GPD) consistently occupy one of the leading places in the structure of dental diseases. Early diagnosis of the initial degree of generalized parodontitis (GP) is an effective way of secondary prevention. This is due to the complexity of understanding the etio-pathogenetic mechanisms of the development generalized parodontal diseases (GPD) and the high association of them with a number of diseases of the internal organs and systems with common points of contact between interdependence and mutual influence, in particular with anorexia nervosa (AN).
View Article and Find Full Text PDFMethylation of the small ribosome subunit rRNA in the ribosomal decoding center results in exceptionally high-level aminoglycoside resistance in bacteria. Enzymes that methylate 16S rRNA on N7 of nucleotide G1405 (mG1405) have been identified in both aminoglycoside-producing and clinically drug-resistant pathogenic bacteria. Using a fluorescence polarization 30S-binding assay and a new crystal structure of the methyltransferase RmtC at 3.
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