7QQ3

Cryo-EM structure of the E.coli 50S ribosomal subunit in complex with the antibiotic Myxovalargin A.

7QQ3 の概要

• エントリーDOI: 10.2210/pdb7qq3/pdb
• EMDBエントリー: 14121
• 関連するBIRD辞書のPRD_ID: PRD_002442
• 分子名称: 23S ribosomal RNA, 50S ribosomal protein L16, 50S ribosomal protein L17, ... (32 entities in total)
• 機能のキーワード: ribosome, antibiotic, myxovalargin a, myxa
• 由来する生物種: Escherichia coli K-12; 詳細
• タンパク質・核酸の鎖数: 29
• 化学式量合計: 1311843.77

構造登録者

Koller, T.O.,Beckert, B.,Wilson, D.N. (登録日: 2022-01-06, 公開日: 2023-01-18, 最終更新日: 2025-03-12)

主引用文献

Koller, T.O.,Scheid, U.,Kosel, T.,Herrmann, J.,Krug, D.,Boshoff, H.I.M.,Beckert, B.,Evans, J.C.,Schlemmer, J.,Sloan, B.,Weiner, D.M.,Via, L.E.,Moosa, A.,Ioerger, T.R.,Graf, M.,Zinshteyn, B.,Abdelshahid, M.,Nguyen, F.,Arenz, S.,Gille, F.,Siebke, M.,Seedorf, T.,Plettenburg, O.,Green, R.,Warnke, A.L.,Ullrich, J.,Warrass, R.,Barry 3rd, C.E.,Warner, D.F.,Mizrahi, V.,Kirschning, A.,Wilson, D.N.,Muller, R.
The Myxobacterial Antibiotic Myxovalargin: Biosynthesis, Structural Revision, Total Synthesis, and Molecular Characterization of Ribosomal Inhibition.
J.Am.Chem.Soc., 145:851-863, 2023

PubMed Abstract: Resistance of bacterial pathogens against antibiotics is declared by WHO as a major global health threat. As novel antibacterial agents are urgently needed, we re-assessed the broad-spectrum myxobacterial antibiotic myxovalargin and found it to be extremely potent against . To ensure compound supply for further development, we studied myxovalargin biosynthesis in detail enabling production via fermentation of a native producer. Feeding experiments as well as functional genomics analysis suggested a structural revision, which was eventually corroborated by the development of a concise total synthesis. The ribosome was identified as the molecular target based on resistant mutant sequencing, and a cryo-EM structure revealed that myxovalargin binds within and completely occludes the exit tunnel, consistent with a mode of action to arrest translation during a late stage of translation initiation. These studies open avenues for structure-based scaffold improvement toward development as an antibacterial agent.

PubMed: 36603206
DOI: 10.1021/jacs.2c08816

実験手法

ELECTRON MICROSCOPY (2.1 Å)