5NDV
Crystal structure of Paromomycin bound to the yeast 80S ribosome
This is a non-PDB format compatible entry.
Summary for 5NDV
| Entry DOI | 10.2210/pdb5ndv/pdb |
| Descriptor | 25S ribosomal RNA, 60S ribosomal protein L8-A, 60S ribosomal protein L9-A, ... (83 entities in total) |
| Functional Keywords | translation, ribosome, 40s, 60s, 80s, eukaryote, rna-protein complex, inhibitor, antibiotic, aminoglycoside, paromomycin |
| Biological source | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) More |
| Cellular location | Cytoplasm : P17076 P05738 P41805 Q3E757 Q12690 P36105 P05748 P26784 P05740 P0CX49 P0CX82 P0CX23 Q02753 P05749 P0CX41 P04449 P04456 P05743 P0C2H6 P02406 P05747 P14120 P0C2H8 P38061 P05744 P87262 P0CX84 P05745 P49166 P49167 P0CX45 P04650 P0CX87 P0CX27 P0CX25 P32905 B3RHV0 P25443 P05750 P14126 P0CX35 P26783 P0CX37 P26786 P0CX39 O13516 Q08745 P0CX47 P48589 P05756 P10664 P39516 Q01855 P0CX51 P02407 P0CX55 P07280 P38701 P0C0V8 P0C0W1 P0CX29 P26321 P0CX31 Q3E792 P39939 P35997 Q3E7X9 P41057 P0CX33 P38011 P39015 P0CX37 Q02326 P05737 Ubiquitin: Cytoplasm . 60S ribosomal protein L40-A: Cytoplasm : P0CH08 |
| Total number of polymer chains | 156 |
| Total formula weight | 6227434.08 |
| Authors | Prokhorova, I.,Djumagulov, M.,Urzhumtsev, A.,Yusupov, M.,Yusupova, G. (deposition date: 2017-03-09, release date: 2017-12-13, Last modification date: 2024-05-08) |
| Primary citation | Prokhorova, I.,Altman, R.B.,Djumagulov, M.,Shrestha, J.P.,Urzhumtsev, A.,Ferguson, A.,Chang, C.T.,Yusupov, M.,Blanchard, S.C.,Yusupova, G. Aminoglycoside interactions and impacts on the eukaryotic ribosome. Proc. Natl. Acad. Sci. U.S.A., 114:E10899-E10908, 2017 Cited by PubMed Abstract: Aminoglycosides are chemically diverse, broad-spectrum antibiotics that target functional centers within the bacterial ribosome to impact all four principle stages (initiation, elongation, termination, and recycling) of the translation mechanism. The propensity of aminoglycosides to induce miscoding errors that suppress the termination of protein synthesis supports their potential as therapeutic interventions in human diseases associated with premature termination codons (PTCs). However, the sites of interaction of aminoglycosides with the eukaryotic ribosome and their modes of action in eukaryotic translation remain largely unexplored. Here, we use the combination of X-ray crystallography and single-molecule FRET analysis to reveal the interactions of distinct classes of aminoglycosides with the 80S eukaryotic ribosome. Crystal structures of the 80S ribosome in complex with paromomycin, geneticin (G418), gentamicin, and TC007, solved at 3.3- to 3.7-Å resolution, reveal multiple aminoglycoside-binding sites within the large and small subunits, wherein the 6'-hydroxyl substituent in ring I serves as a key determinant of binding to the canonical eukaryotic ribosomal decoding center. Multivalent binding interactions with the human ribosome are also evidenced through their capacity to affect large-scale conformational dynamics within the pretranslocation complex that contribute to multiple aspects of the translation mechanism. The distinct impacts of the aminoglycosides examined suggest that their chemical composition and distinct modes of interaction with the ribosome influence PTC read-through efficiency. These findings provide structural and functional insights into aminoglycoside-induced impacts on the eukaryotic ribosome and implicate pleiotropic mechanisms of action beyond decoding. PubMed: 29208708DOI: 10.1073/pnas.1715501114 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.3 Å) |
Structure validation
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