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

これはPDB形式変換不可エントリーです。

9D0H の概要

• エントリーDOI: 10.2210/pdb9d0h/pdb
• 分子名称: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (61 entities in total)
• 機能のキーワード: cresomycin glycosides; lincosamides; structure-based drug design; antibiotic; 70s ribosome; x-ray structure; inhibition of translation; peptidyl transferase center; nascent peptide exit tunnel, ribosome
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 112
• 化学式量合計: 4571468.57

構造登録者

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. (登録日: 2024-08-07, 公開日: 2025-08-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.5 Å)