絞り込み

16590

広告

Deciphering Determinants in Ribosomal Methyltransferases that Confer Antimicrobial Resistance.

著者 Bhujbalrao R , Anand R
J Am Chem Soc.2019 Jan 09 ; ():.
この記事をPubMed上で見るPubMedで表示
この記事をGoogle翻訳上で見る Google翻訳で開く

スターを付ける スターを付ける     (3view , 0users)

Full Text Sources

Post-translational methylation of ribosomal RNA at select positions is a prevalent resistance mechanism adopted by pathogens. In this work, KsgA, a housekeeping ribosomal methyltransferase (rMtase) involved in ribosome biogenesis, was exploited as a model system to delineate the specific targeting determinants that impart substrate specificity to rMtases. With a combination of evolutionary and structure-guided approaches, a set of chimeras were created that altered the targeting specificity of KsgA such that it acted similarly to erythromycin-resistant methyltransferases (Erms), rMtases found in multidrug-resistant pathogens. The results revealed that specific loop embellishments on the basic Rossmann fold are key determinants in the selection of the cognate RNA. Moreover, in vivo studies confirmed that chimeric constructs are competent in imparting macrolide resistance. This work explores the factors that govern the emergence of resistance and paves the way for the design of specific inhibitors useful in reversing antibiotic resistance.
PMID: 30624914 [PubMed - as supplied by publisher]
印刷用ページを開く Endnote用テキストダウンロード