Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Export

@article{citeulike:222735, abstract = {Ribosomes, the site of protein synthesis, are a major target for natural and synthetic antibiotics. Detailed knowledge of antibiotic binding sites is central to understanding the mechanisms of drug action. Conversely, drugs are excellent tools for studying the ribosome function. To elucidate the structural basis of ribosome-antibiotic interactions, we determined the high-resolution X-ray structures of the 50S ribosomal subunit of the eubacterium Deinococcus radiodurans, complexed with the clinically relevant antibiotics chloramphenicol, clindamycin and the three macrolides erythromycin, clarithromycin and roxithromycin. We found that antibiotic binding sites are composed exclusively of segments of 23S ribosomal RNA at the peptidyl transferase cavity and do not involve any interaction of the drugs with ribosomal proteins. Here we report the details of antibiotic interactions with the components of their binding sites. Our results also show the importance of putative Mg+2 ions for the binding of some drugs. This structural analysis should facilitate rational drug design.}, address = {Max-Planck-Research, Unit for Ribosomal Structure, Notkestrasse 85, 22603 Hamburg, Germany.}, author = {Schl\"{u}nzen, F. and Zarivach, R. and Harms, J. and Bashan, A. and Tocilj, A. and Albrecht, R. and Yonath, A. and Franceschi, F.}, citeulike-article-id = {222735}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/35101544}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/413814a0}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/11677599}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=11677599}, day = {25}, doi = {10.1038/35101544}, issn = {0028-0836}, journal = {Nature}, keywords = {antibiotics, docking, pharmacology, protein, structure}, month = {October}, number = {6858}, pages = {814--821}, posted-at = {2005-06-08 14:28:12}, priority = {5}, title = {Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria.}, url = {http://dx.doi.org/10.1038/35101544}, volume = {413}, year = {2001} }

TY - JOUR ID - citeulike:222735 L3 - citeulike-article-id:222735 N2 - Ribosomes, the site of protein synthesis, are a major target for natural and synthetic antibiotics. Detailed knowledge of antibiotic binding sites is central to understanding the mechanisms of drug action. Conversely, drugs are excellent tools for studying the ribosome function. To elucidate the structural basis of ribosome-antibiotic interactions, we determined the high-resolution X-ray structures of the 50S ribosomal subunit of the eubacterium Deinococcus radiodurans, complexed with the clinically relevant antibiotics chloramphenicol, clindamycin and the three macrolides erythromycin, clarithromycin and roxithromycin. We found that antibiotic binding sites are composed exclusively of segments of 23S ribosomal RNA at the peptidyl transferase cavity and do not involve any interaction of the drugs with ribosomal proteins. Here we report the details of antibiotic interactions with the components of their binding sites. Our results also show the importance of putative Mg+2 ions for the binding of some drugs. This structural analysis should facilitate rational drug design. IS - 6858 JF - Nature SN - 0028-0836 AD - Max-Planck-Research, Unit for Ribosomal Structure, Notkestrasse 85, 22603 Hamburg, Germany. EP - 821 TI - Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. VL - 413 SP - 814 KW - antibiotics KW - docking KW - pharmacology KW - protein KW - structure AU - Schlünzen, F AU - Zarivach, R AU - Harms, J AU - Bashan, A AU - Tocilj, A AU - Albrecht, R AU - Yonath, A AU - Franceschi, F PY - 2001/10/25/ UR - http://dx.doi.org/10.1038/35101544 ER -