| Structural highlights
8vtw is a 20 chain structure with sequence from Thermus thermophilus HB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.35Å |
| Ligands: | , , , , , , , , , , , , , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
RL2_THET8 One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial (By similarity). Makes several contacts with the 16S rRNA (forming bridge B7b) in the 70S ribosome.[HAMAP-Rule:MF_01320_B]
Publication Abstract from PubMed
Growing resistance toward ribosome-targeting macrolide antibiotics has limited their clinical utility and urged the search for superior compounds. Macrolones are synthetic macrolide derivatives with a quinolone side chain, structurally similar to DNA topoisomerase-targeting fluoroquinolones. While macrolones show enhanced activity, their modes of action have remained unknown. Here, we present the first structures of ribosome-bound macrolones, showing that the macrolide part occupies the macrolide-binding site in the ribosomal exit tunnel, whereas the quinolone moiety establishes new interactions with the tunnel. Macrolones efficiently inhibit both the ribosome and DNA topoisomerase in vitro. However, in the cell, they target either the ribosome or DNA gyrase or concurrently both of them. In contrast to macrolide or fluoroquinolone antibiotics alone, dual-targeting macrolones are less prone to select resistant bacteria carrying target-site mutations or to activate inducible macrolide resistance genes. Furthermore, because some macrolones engage Erm-modified ribosomes, they retain activity even against strains with constitutive erm resistance genes.
Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms.,Aleksandrova EV, Ma CX, Klepacki D, Alizadeh F, Vazquez-Laslop N, Liang JH, Polikanov YS, Mankin AS Nat Chem Biol. 2024 Jul 22. doi: 10.1038/s41589-024-01685-3. PMID:39039256[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Aleksandrova EV, Ma CX, Klepacki D, Alizadeh F, Vázquez-Laslop N, Liang JH, Polikanov YS, Mankin AS. Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms. Nat Chem Biol. 2024 Jul 22. PMID:39039256 doi:10.1038/s41589-024-01685-3
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