4U4R
Crystal structure of Lactimidomycin bound to the yeast 80S ribosome
This is a non-PDB format compatible entry.
Summary for 4U4R
| Entry DOI | 10.2210/pdb4u4r/pdb |
| Descriptor | 18S ribosomal RNA, 40S ribosomal protein S8-A, 40S ribosomal protein S9-A, ... (88 entities in total) |
| Functional Keywords | translation, ribosome, 40s, 60s, 80s, eukaryote, rna-protein complex, inhibitor, antibiotic |
| Biological source | Saccharomyces cerevisiae S288c More |
| Total number of polymer chains | 162 |
| Total formula weight | 6631767.24 |
| Authors | Garreau de Loubresse, N.,Prokhorova, I.,Yusupova, G.,Yusupov, M. (deposition date: 2014-07-24, release date: 2014-10-22, Last modification date: 2024-10-09) |
| Primary citation | Garreau de Loubresse, N.,Prokhorova, I.,Holtkamp, W.,Rodnina, M.V.,Yusupova, G.,Yusupov, M. Structural basis for the inhibition of the eukaryotic ribosome. Nature, 513:517-522, 2014 Cited by PubMed Abstract: The ribosome is a molecular machine responsible for protein synthesis and a major target for small-molecule inhibitors. Compared to the wealth of structural information available on ribosome-targeting antibiotics in bacteria, our understanding of the binding mode of ribosome inhibitors in eukaryotes is currently limited. Here we used X-ray crystallography to determine 16 high-resolution structures of 80S ribosomes from Saccharomyces cerevisiae in complexes with 12 eukaryote-specific and 4 broad-spectrum inhibitors. All inhibitors were found associated with messenger RNA and transfer RNA binding sites. In combination with kinetic experiments, the structures suggest a model for the action of cycloheximide and lactimidomycin, which explains why lactimidomycin, the larger compound, specifically targets the first elongation cycle. The study defines common principles of targeting and resistance, provides insights into translation inhibitor mode of action and reveals the structural determinants responsible for species selectivity which could guide future drug development. PubMed: 25209664DOI: 10.1038/nature13737 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.801 Å) |
Structure validation
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