5LKS
Structure-function insights reveal the human ribosome as a cancer target for antibiotics
This is a non-PDB format compatible entry.
Summary for 5LKS
| Entry DOI | 10.2210/pdb5lks/pdb |
| EMDB information | 4070 |
| Descriptor | 28S ribosomal RNA, 60S ribosomal protein L7a, 60S ribosomal protein L9, ... (84 entities in total) |
| Functional Keywords | cryoem, human ribosome, 80s, cycloheximide, ribosome |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 80 |
| Total formula weight | 3818879.56 |
| Authors | Myasnikov, A.G.,Natchiar, S.K.,Nebout, M.,Hazemann, I.,Imbert, V.,Khatter, H.,Peyron, J.-F.,Klaholz, B.P. (deposition date: 2016-07-23, release date: 2017-04-26, Last modification date: 2019-12-11) |
| Primary citation | 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 Cited by 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: 27665925DOI: 10.1038/ncomms12856 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.6 Å) |
Structure validation
Download full validation report
