9D0H

Crystal structure of the wild-type Thermus thermophilus 70S ribosome in complex with C-cresomycin, mRNA, deacylated A-site tRNAphe, aminoacylated P-site fMet-tRNAmet, and deacylated E-site tRNAphe at 2.50A resolution

This is a non-PDB format compatible entry.

Summary for 9D0H

• Entry DOI: 10.2210/pdb9d0h/pdb
• Descriptor: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (61 entities in total)
• Functional Keywords: cresomycin glycosides; lincosamides; structure-based drug design; antibiotic; 70s ribosome; x-ray structure; inhibition of translation; peptidyl transferase center; nascent peptide exit tunnel, ribosome
• Biological source: Escherichia coli; More
• Total number of polymer chains: 112
• Total formula weight: 4571468.57

Authors

Aleksandrova, E.V.,Wu, K.J.Y.,Robinson, P.J.,Benedetto, A.E.,Yu, M.,Tresco, B.I.C.,See, D.N.Y.,Jiang, T.,Ramkissoon, A.,Dunand, C.F.,Svetlov, M.S.,Lee, J.,Myers, A.G.,Polikanov, Y.S. (deposition date: 2024-08-07, release date: 2025-08-27)

Primary citation

Wu, K.J.Y.,Aleksandrova, E.V.,Robinson, P.J.,Benedetto, A.E.,Yu, M.,Tresco, B.I.C.,See, D.N.Y.,Jiang, T.,Ramkissoon, A.,Dunand, C.F.,Svetlov, M.S.,Lee, J.,Polikanov, Y.S.,Myers, A.G.
Why Sulfur is Important in Lincosamide Antibiotics.
Chem, 11:-, 2025

PubMed Abstract: We recently reported the conception and synthesis of cresomycin (), a fully synthetic lincosamide antibiotic effective in vitro and in vivo against multidrug-resistant Gram-positive and Gram-negative bacteria. In this work, we describe the chemical synthesis and characterization of sulfur atom replacement analogs (S → CH), (S → O), and (S → Se). Comparison of high-resolution co-crystal structures showed that the four analogs adopted identical conformations when bound to the bacterial ribosome, but due to variations of ≤1 Å in the bond lengths between the anomeric carbon and the varied atoms, only the and heteroatoms of and , respectively, were positioned to interact with the π-face of nucleobase G2505. and did not benefit from such stabilizations, with correspondingly negative consequences in both target engagement and antibacterial activities. We therefore conclude that the sulfur atom of the lincosamides is important in ribosomal binding.

PubMed: 40787583
DOI: 10.1016/j.chempr.2025.102480

Experimental method

X-RAY DIFFRACTION (2.5 Å)