title: Influence of thiostrepton binding on the ribosomal GTPase associated region characterized by molecular dynamics simulation.
abstract: The thiostrepton antibiotic inhibits bacterial protein synthesis by binding to a cleft formed by the ribosomal protein L11 and 23S's rRNA helices 43-44 on the 70S ribosome. It was proposed from crystal structures that the ligand restricts L11's N-terminal movement and thus prevents proper translation factor binding. An exact understanding of thiostrepton's impact on the binding site's dynamics at atomistic resolution is still missing. Here we report an all-atom molecular dynamics simulations of the binary L11·rRNA and the ternary L11·rRNA·thiostrepton complex (rRNA = helices 43-44). We demonstrate that thiostrepton directly impacts the binding site's atomic and biomacromolecular dynamics.
authors.affiliation: Department of Bioinformatics, Fraunhofer-Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, 53754 Sankt Augustin, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Wolf
authors.forename: Sascha
authors.initials: S
authors.lastname: Baumann
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Arndt
authors.forename: Karl N
authors.initials: KN
authors.lastname: Kirschner
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012335:RNA, Ribosomal / Q000737:chemistry / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects / Q000201:enzymology*; D013883:Thiostrepton / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; C027624:ribosomal protein L11; D020558:GTP Phosphohydrolases; D013883:Thiostrepton