Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Université de Strasbourg, 67404, Illkirch, France
- Nicolas Garreau de Loubresse,
- Irina Prokhorova,
- Gulnara Yusupova &
- Marat Yusupov
Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany
- Wolf Holtkamp &
- Marina V. Rodnina
M.Y. supervised the study. N.G.D.L. designed the experiments. N.G.D.L. and I.P. conducted purification, crystallization and post-crystallization treatment experiments, collected X-ray diffraction data and carried out the structure determination. N.G.D.L., I.P., G.Y. and M.Y. analysed the crystal structures. M.V.R. and W.H. designed, performed and interpreted rapid kinetic experiments. N.G.D.L. wrote the initial manuscript to which M.V.R., G.Y. and M.Y. contributed specialist insights. All authors helped with refining the manuscript and approved the final version.
Competing financial interests
The authors declare no competing financial interests.
Atomic coordinates and structure factors for the reported crystal structures have been deposited in the Protein Data Bank (http://www.pdb.org/pdb/home/home.do) under accession codes 4U3M (anisomycin), 4U56 (blasticidin S), 4U3N (CCA), 4U55 (cryptopleurine), 4U3U (cycloheximide), 4U53 (deoxynivalenol), 4U4N (edeine), 4U4O (geneticin G418), 4U4Q (homoharringtonine), 4U4R (lactimidomycin), 4U4U (lycorine), 4U52 (nagilactone C), 4U51 (narcilasine), 4U4Y (pactamycin), 4U4Z (phyllanthoside), 4U6F (T-2 toxin) and 4U50 (verrucarin).
Nicolas Garreau de Loubresse
Marina V. Rodnina
Extended Data Figure 1: Unbiased positive electron density of small-molecule inhibitors and CCA-trinucleotide.Hover over figure to zoom
Extended Data Figure 2: Electron density of small-molecule inhibitors and CCA-trinucleotide.Hover over figure to zoom
Extended Data Figure 3: Structures of homoharringtonine, anisomycin, blasticidin S and pactamycin in eukaryotes, archaea and bacteria.Hover over figure to zoom
Extended Data Figure 4: Structural differences in protein eL42 may preclude the binding of lactimidomycin and phyllanthoside to the archaeal ribosome.Hover over figure to zoom
Extended Data Figure 5: Close-up view of CCA tri-nucleotide binding site.Hover over figure to zoom
Extended Data Figure 6: Kinetic study of lactimidomycin and cycloheximide.Hover over figure to zoom
Extended Data Figure 7: Close-up view of blasticidin S binding site.Hover over figure to zoom
Extended Data Figure 8: Conformational changes in the peptidyl transferase centre and differences with the archaeal ribosome.Hover over figure to zoom
Extended Data Table 1: Summary of information for the 16 small-molecule inhibitorsHover over figure to zoom
Extended Data Table 2: Resistant mutations in proteins of the yeast ribosomeHover over figure to zoom