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-Structure paper
タイトル | Structure-function insights reveal the human ribosome as a cancer target for antibiotics. |
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ジャーナル・号・ページ | Nat Commun, Vol. 7, Page 12856, Year 2016 |
掲載日 | 2016年9月26日 |
著者 | Alexander G Myasnikov / S Kundhavai Natchiar / Marielle Nebout / Isabelle Hazemann / Véronique Imbert / Heena Khatter / Jean-François Peyron / Bruno P Klaholz / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:27665925 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.6 Å |
構造データ | |
化合物 | ChemComp-3HE: ChemComp-MG: ChemComp-ZN: ChemComp-HOH: |
由来 |
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キーワード | RIBOSOME / CryoEM / human ribosome / 80S / cycloheximide |