Movie
Controller
Structure viewers
About Yorodumi Papers
+Search query
-Structure paper
| Title | Cryo-EM structures reveal the molecular mechanism of HflX-mediated erythromycin resistance in mycobacteria. |
|---|---|
| Journal, issue, pages | Structure, Year 2024 |
| Publish date | Jul 8, 2024 |
 Authors | Krishnamoorthi Srinivasan / Aneek Banerjee / Jayati Sengupta /  |
| PubMed Abstract | Mycobacterial HflX confers resistance against macrolide antibiotics. However, the exact molecular mechanism is poorly understood. To gain further insights, we determined the cryo-EM structures of M. ...Mycobacterial HflX confers resistance against macrolide antibiotics. However, the exact molecular mechanism is poorly understood. To gain further insights, we determined the cryo-EM structures of M. smegmatis (Msm) HflX-50S subunit and 50S subunit-erythromycin (ERY) complexes at a global resolution of approximately 3 Å. A conserved nucleotide A2286 at the gate of nascent peptide exit tunnel (NPET) adopts a swayed conformation in HflX-50S complex and interacts with a loop within the linker helical (LH) domain of MsmHflX that contains an additional 9 residues insertion. Interestingly, the swaying of this nucleotide, which is usually found in the non-swayed conformation, is induced by erythromycin binding. Furthermore, we observed that erythromycin decreases HflX's ribosome-dependent GTP hydrolysis, resulting in its enhanced binding and anti-association activity on the 50S subunit. Our findings reveal how mycobacterial HflX senses the presence of macrolides at the peptide tunnel entrance and confers antibiotic resistance in mycobacteria. |
 External links | Structure / PubMed:39029461 |
| Methods | EM (single particle) |
| Resolution | 3.3 - 3.6 Å |
| Structure data | EMDB-37007, PDB-8kab: EMDB-38788, PDB-8xz3: |
| Chemicals |  ChemComp-GNP:  ChemComp-ERY: |
| Source |
|
 Keywords | RIBOSOME / Complex / Antibiotic |
mycolicibacterium smegmatis mc2 155 (bacteria)