5LKS

Structure-function insights reveal the human ribosome as a cancer target for antibiotics

これはPDB形式変換不可エントリーです。

5LKS の概要

• エントリーDOI: 10.2210/pdb5lks/pdb
• EMDBエントリー: 4070
• 分子名称: 28S ribosomal RNA, 60S ribosomal protein L7a, 60S ribosomal protein L9, ... (84 entities in total)
• 機能のキーワード: cryoem, human ribosome, 80s, cycloheximide, ribosome
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 80
• 化学式量合計: 3818879.56

構造登録者

Myasnikov, A.G.,Natchiar, S.K.,Nebout, M.,Hazemann, I.,Imbert, V.,Khatter, H.,Peyron, J.-F.,Klaholz, B.P. (登録日: 2016-07-23, 公開日: 2017-04-26, 最終更新日: 2025-10-01)

主引用文献

Myasnikov, A.G.,Kundhavai Natchiar, S.,Nebout, M.,Hazemann, I.,Imbert, V.,Khatter, H.,Peyron, J.F.,Klaholz, B.P.
Structure-function insights reveal the human ribosome as a cancer target for antibiotics.
Nat Commun, 7:12856-12856, 2016

PubMed Abstract: Many antibiotics in clinical use target the bacterial ribosome by interfering with the protein synthesis machinery. However, targeting the human ribosome in the case of protein synthesis deregulations such as in highly proliferating cancer cells has not been investigated at the molecular level up to now. Here we report the structure of the human 80S ribosome with a eukaryote-specific antibiotic and show its anti-proliferative effect on several cancer cell lines. The structure provides insights into the detailed interactions in a ligand-binding pocket of the human ribosome that are required for structure-assisted drug design. Furthermore, anti-proliferative dose response in leukaemic cells and interference with synthesis of c-myc and mcl-1 short-lived protein markers reveals specificity of a series of eukaryote-specific antibiotics towards cytosolic rather than mitochondrial ribosomes, uncovering the human ribosome as a promising cancer target.

PubMed: 27665925
DOI: 10.1038/ncomms12856

実験手法

ELECTRON MICROSCOPY (3.6 Å)