5lks | pdb_00005lks

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

Loading... Status: waiting for Mol* initialization Structural highlights 5lks is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.6Å Ligands: 3HE, MG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RL18A_HUMAN Publication Abstract from PubMed 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. Structure-function insights reveal the human ribosome as a cancer target for antibiotics.,Myasnikov AG, Kundhavai Natchiar S, Nebout M, Hazemann I, Imbert V, Khatter H, Peyron JF, Klaholz BP Nat Commun. 2016 Sep 26;7:12856. doi: 10.1038/ncomms12856. PMID:27665925 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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