 |
PDBsum entry 6ift
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Deciphering determinants in ribosomal methyltransferases that confer antimicrobial resistance.
|
|
|
Authors
|
|
R.Bhujbalrao,
R.Anand.
|
|
|
Ref.
|
|
J Am Chem Soc, 2019,
141,
1425-1429.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
