Sengupta, Sombuddha and Mukherjee, Rajat and Pilsl, Michael and Bagale, Siddharam and Adhikary, Arijit Das and Borkar, Aditi N. and Pradeepkumar, Pushpangadan Indira and Engel, Christoph and Chowdhury, Arindam and Kaushal, Prem S. and Anand, Ruchi (2025) Mechanistic insights into 50S precursor recognition and targeting by erythromycin resistance methyltransferase. SCIENCE ADVANCES, 11 (48): eaea1545. ISSN 2375-2548
Full text not available from this repository. (Request a copy)Abstract
Erythromycin resistance methyltransferases (Erms) confer resistance to macrolide, lincosamide, and streptogramin B antibiotics by methylating an internal base (A2058, E. coli numbering) in an elusive precursor ribosomal state. Here, we capture the 50S ribosomal precursor-Erm complex by cryo-EM and show that a transient pocket formed in the early steps of ribosome biogenesis, situated 35 angstrom from the methylation site, serves as an anchor for the auxiliary C-terminal domain of Erm, thereby playing a crucial role in achieving specificity in this short-lived substrate with evolving structural features. Cryo-EM reveals that the catalytic Rossman fold of Erm undergoes a swaying motion to facilitate substrate scouting. Corroboratory smFRET studies show that for effective catalysis, Erm transitions between multiple conformations, an effective strategy adopted to orient the dynamic helix where methylation occurs. Unraveling this unique mechanism of targeting adopted by Erm paves the way for selective design of allosteric inhibitors directed toward reversing MLSB resistance.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RIBOSOMAL-RNA; ERMC METHYLTRANSFERASE; SINGLE METHYLATION; SUBUNIT; DNA; COMPLEX; BINDING; SITE; LINCOSAMIDES; INHIBITORS |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie III |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Aug 2026 06:38 |
| Last Modified: | 11 Aug 2026 06:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/66998 |
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