The structures of four macrolide antibiotics bound to the large ribosomal subunit. Export

@article{citeulike:222741, abstract = {Crystal structures of the Haloarcula marismortui large ribosomal subunit complexed with the 16-membered macrolide antibiotics carbomycin A, spiramycin, and tylosin and a 15-membered macrolide, azithromycin, show that they bind in the polypeptide exit tunnel adjacent to the peptidyl transferase center. Their location suggests that they inhibit protein synthesis by blocking the egress of nascent polypeptides. The saccharide branch attached to C5 of the lactone rings extends toward the peptidyl transferase center, and the isobutyrate extension of the carbomycin A disaccharide overlaps the A-site. Unexpectedly, a reversible covalent bond forms between the ethylaldehyde substituent at the C6 position of the 16-membered macrolides and the N6 of A2103 (A2062, E. coli). Mutations in 23S rRNA that result in clinical resistance render the binding site less complementary to macrolides.}, address = {Department of Molecular Biophysics and Biochemistry, New Haven, Connecticut 06520, USA.}, author = {Hansen, J. L. and Ippolito, J. A. and Ban, N. and Nissen, P. and Moore, P. B. and Steitz, T. A.}, citeulike-article-id = {222741}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/12150912}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=12150912}, issn = {1097-2765}, journal = {Mol Cell}, keywords = {antibiotics, docking, pharmacology, protein, structure}, month = {July}, number = {1}, pages = {117--128}, posted-at = {2005-06-08 15:10:23}, priority = {5}, title = {The structures of four macrolide antibiotics bound to the large ribosomal subunit.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/12150912}, volume = {10}, year = {2002} }

TY - JOUR ID - citeulike:222741 L3 - citeulike-article-id:222741 N2 - Crystal structures of the Haloarcula marismortui large ribosomal subunit complexed with the 16-membered macrolide antibiotics carbomycin A, spiramycin, and tylosin and a 15-membered macrolide, azithromycin, show that they bind in the polypeptide exit tunnel adjacent to the peptidyl transferase center. Their location suggests that they inhibit protein synthesis by blocking the egress of nascent polypeptides. The saccharide branch attached to C5 of the lactone rings extends toward the peptidyl transferase center, and the isobutyrate extension of the carbomycin A disaccharide overlaps the A-site. Unexpectedly, a reversible covalent bond forms between the ethylaldehyde substituent at the C6 position of the 16-membered macrolides and the N6 of A2103 (A2062, E. coli). Mutations in 23S rRNA that result in clinical resistance render the binding site less complementary to macrolides. IS - 1 JF - Mol Cell SN - 1097-2765 AD - Department of Molecular Biophysics and Biochemistry, New Haven, Connecticut 06520, USA. EP - 128 TI - The structures of four macrolide antibiotics bound to the large ribosomal subunit. VL - 10 SP - 117 KW - antibiotics KW - docking KW - pharmacology KW - protein KW - structure AU - Hansen, JL AU - Ippolito, JA AU - Ban, N AU - Nissen, P AU - Moore, PB AU - Steitz, TA PY - 2002/07// UR - http://view.ncbi.nlm.nih.gov/pubmed/12150912 ER -