6IFT
KsgA from Bacillus subtilis in complex with SAM
Summary for 6IFT
| Entry DOI | 10.2210/pdb6ift/pdb |
| Descriptor | Ribosomal RNA small subunit methyltransferase A, S-ADENOSYLMETHIONINE (3 entities in total) |
| Functional Keywords | ksga, sam, methyltransferase, resistance, transferase |
| Biological source | Bacillus subtilis (strain 168) |
| Total number of polymer chains | 1 |
| Total formula weight | 33158.37 |
| Authors | Bhujbalrao, R.,Anand, R. (deposition date: 2018-09-21, release date: 2019-01-30, Last modification date: 2024-03-27) |
| Primary citation | Bhujbalrao, R.,Anand, R. Deciphering Determinants in Ribosomal Methyltransferases That Confer Antimicrobial Resistance. J. Am. Chem. Soc., 141:1425-1429, 2019 Cited by 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: 30624914DOI: 10.1021/jacs.8b10277 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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