6IFX

Crystal structure of chimeric KsgA with loop 12 from Erm

6IFX の概要

• エントリーDOI: 10.2210/pdb6ifx/pdb
• 分子名称: Ribosomal RNA small subunit methyltransferase A (2 entities in total)
• 機能のキーワード: chimera, resistance, ksga, transferase
• 由来する生物種: Bacillus subtilis (strain 168); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 64651.12

構造登録者

Bhujbalrao, R.,Anand, R. (登録日: 2018-09-21, 公開日: 2019-02-06, 最終更新日: 2024-03-27)

主引用文献

Bhujbalrao, R.,Anand, R.
Deciphering Determinants in Ribosomal Methyltransferases That Confer Antimicrobial Resistance.
J. Am. Chem. Soc., 141:1425-1429, 2019

PubMed Abstract: Post-translational methylation of rRNA 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.

PubMed: 30624914
DOI: 10.1021/jacs.8b10277

実験手法

X-RAY DIFFRACTION (3.8 Å)