9J1M

KU13-bond Mycobacterium tuberculosis 70S ribosome

This is a non-PDB format compatible entry.

Summary for 9J1M

• Entry DOI: 10.2210/pdb9j1m/pdb
• EMDB information: 61076
• Descriptor: Large ribosomal subunit protein bL32, Large ribosomal subunit protein uL3, Large ribosomal subunit protein uL4, ... (55 entities in total)
• Functional Keywords: ribosome, macrolide, antibiotic, ribosome-antibiotic complex, ribosome/antibiotic
• Biological source: Mycobacterium tuberculosis variant bovis BCG str. Pasteur 1173P2; More
• Total number of polymer chains: 52
• Total formula weight: 2247404.10

Authors

Nishihara, D.,Fujino, M.,Tanaka, Y.,Yokoyama, T. (deposition date: 2024-08-05, release date: 2025-03-19)

Primary citation

Isozaki, Y.,Makikawa, T.,Kimura, K.,Nishihara, D.,Fujino, M.,Tanaka, Y.,Hayashi, C.,Ishizaki, Y.,Igarashi, M.,Yokoyama, T.,Toshima, K.,Takahashi, D.
Creation of a macrolide antibiotic against non-tuberculous Mycobacterium using late-stage boron-mediated aglycon delivery.
Sci Adv, 11:eadt2352-eadt2352, 2025

PubMed Abstract: Non-tuberculous mycobacteria (NTM) is gaining clinical recognition as a recently emerging pulmonary pathogen. complex (MAC), the most common NTM, is the cause of pulmonary MAC disease. Currently, the macrolide azithromycin (AZM) is the standard first-line antibiotic for treatment of the disease. However, the rise of drug-resistant MAC necessitates the development of alternative therapeutics. Here, we present a late-stage boron-mediated aglycon delivery strategy for selective modification of AZM, generating a library of potential anti-MAC drugs designated to . Screening of to revealed that exhibited enhanced antimicrobial activity against wild-type and macrolide-resistant MAC compared to AZM. Cryo-electron microscopy analysis indicated that the inserted tercyclic moiety of formed a robust anchor on the bacterial ribosome, creating a binding pocket with base flipping of U2847, potentially bypassing the standard mechanism of macrolide resistance. These results position as a promising lead for therapeutics against macrolide-resistant MAC.

PubMed: 40043128
DOI: 10.1126/sciadv.adt2352

Experimental method

ELECTRON MICROSCOPY (2.33 Å)