title: Structural basis for potent inhibitory activity of the antibiotic tigecycline during protein synthesis.
abstract: Here we present an X-ray crystallography structure of the clinically relevant tigecycline antibiotic bound to the 70S ribosome. Our structural and biochemical analysis indicate that the enhanced potency of tigecycline results from a stacking interaction with nucleobase C1054 within the decoding site of the ribosome. Single-molecule fluorescence resonance energy transfer studies reveal that, during decoding, tigecycline inhibits the initial codon recognition step of tRNA accommodation and prevents rescue by the tetracycline-resistance protein TetM.
authors: Institut National de la Santé et de la Recherche Médicale U964, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7104, 67404 Illkirch, France.
authors: Lasse
authors: L
authors: Jenner
authors: Agata L
authors: AL
authors: Starosta
authors: Daniel S
authors: DS
authors: Terry
authors: Aleksandra
authors: A
authors: Mikolajka
authors: Liudmila
authors: L
authors: Filonava
authors: Marat
authors: M
authors: Yusupov
authors: Scott C
authors: SC
authors: Blanchard
authors: Daniel N
authors: DN
authors: Wilson
authors: Gulnara
authors: G
authors: Yusupova
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D031541:Fluorescence Resonance Energy Transfer; D006033:Glycylglycine / Q000737:chemistry / Q000494:pharmacology; D008911:Minocycline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D014176:Protein Biosynthesis / Q000187:drug effects; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D055672:Static Electricity; D013329:Structure-Activity Relationship; D016963:Thermus thermophilus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial; D006033:Glycylglycine; D000078304:Tigecycline; D012343:RNA, Transfer; D008911:Minocycline