4W2I
Crystal structure of the Thermus thermophilus 70S ribosome in complex with negamycin, mRNA and three deacylated tRNAs in the A, P and E sites
This is a non-PDB format compatible entry.
Summary for 4W2I
| Entry DOI | 10.2210/pdb4w2i/pdb |
| Descriptor | 16S Ribosomal RNA, 30S Ribosomal Protein S10, 30S Ribosomal Protein S11, ... (61 entities in total) |
| Functional Keywords | negamycin, antibiotic, 70s ribosome, inhibition of translation, miscoding, translocation inhibitor, 30s subunit with negamycin, mrna, deacylated a-, p-, and e-site trnas of the 1st 70s ribosome in the asu, functional complex of bacterial 70s ribosome with antibiotic negamycin, 50s subunit of the 1st 70s ribosome in the asu, ribosome-antibiotic complex, ribosome/antibiotic |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 112 |
| Total formula weight | 4555287.71 |
| Authors | Polikanov, Y.S.,Szal, T.,Jiang, F.,Gupta, P.,Matsuda, R.,Shiozuka, M.,Steitz, T.A.,Vazquez-Laslop, N.,Mankin, A.S. (deposition date: 2014-09-12, release date: 2014-10-15, Last modification date: 2023-12-27) |
| Primary citation | Polikanov, Y.S.,Szal, T.,Jiang, F.,Gupta, P.,Matsuda, R.,Shiozuka, M.,Steitz, T.A.,Vazquez-Laslop, N.,Mankin, A.S. Negamycin Interferes with Decoding and Translocation by Simultaneous Interaction with rRNA and tRNA. Mol.Cell, 56:541-550, 2014 Cited by PubMed Abstract: Negamycin (NEG) is a ribosome-targeting antibiotic that exhibits clinically promising activity. Its binding site and mode of action have remained unknown. We solved the structure of the Thermus thermophilus ribosome bound to mRNA and three tRNAs, in complex with NEG. The drug binds to both small and large ribosomal subunits at nine independent sites. Resistance mutations in the 16S rRNA unequivocally identified the binding site in the vicinity of the conserved helix 34 (h34) in the small subunit as the primary site of antibiotic action in the bacterial and, possibly, eukaryotic ribosome. At this site, NEG contacts 16S rRNA as well as the anticodon loop of the A-site tRNA. Although the NEG site of action overlaps with that of tetracycline (TET), the two antibiotics exhibit different activities: while TET sterically hinders binding of aminoacyl-tRNA to the ribosome, NEG stabilizes its binding, thereby inhibiting translocation and stimulating miscoding. PubMed: 25306922DOI: 10.1016/j.molcel.2014.09.021 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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