9B4Z
E. coli 70S ribosome complex (N1-methylated 16S A1408 + arbekacin)
This is a non-PDB format compatible entry.
Summary for 9B4Z
| Entry DOI | 10.2210/pdb9b4z/pdb |
| EMDB information | 44192 |
| Descriptor | 16S ribosomal RNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (58 entities in total) |
| Functional Keywords | aminoglycoside, a1408, resistance, ribosome |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 56 |
| Total formula weight | 2249966.58 |
| Authors | Mattingly, J.M.,Dey, D.,Zelinskaya, N.,Dunham, C.M.,Conn, G.L. (deposition date: 2024-03-21, release date: 2025-08-27, Last modification date: 2025-09-10) |
| Primary citation | Dey, D.,Mattingly, J.M.,Zelinskaya, N.,Dunham, C.M.,Conn, G.L. Basis for selective drug evasion of an aminoglycoside-resistance ribosomal RNA modification. Nat Commun, 16:7992-7992, 2025 Cited by PubMed Abstract: Aminoglycosides disrupt the fidelity of bacterial protein synthesis, but their potent antibacterial activity is threatened by multiple resistance mechanisms, including methylation of their ribosomal RNA (rRNA) binding site. However, the impact of one such resistance-conferring methylation on N1 of helix 44 nucleotide A1408 (mA1408) is highly variable with some aminoglycosides retaining significant potency. Here, we examine bacterial susceptibility to diverse aminoglycosides, determine high-resolution electron cryomicroscopy structures of mA1408-modified 70S ribosome-aminoglycoside complexes, and perform molecular dynamics simulations to decipher the key determinants of such "resistance evasion." Collectively, these analyses reveal how some aminoglycosides adapt their conformation to accommodate mA1408, including the roles of specific ring substituents, balancing ligand strain and maintaining favorable interactions, as well as interactions made by additional functional groups that compensate for those disrupted by the modification. This work provides design principles that can guide future rational development of aminoglycosides refractory to resistance conferred by rRNA modifications. PubMed: 40866347DOI: 10.1038/s41467-025-63278-5 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.2 Å) |
Structure validation
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