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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology*
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Base Sequence
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Binding Sites
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Crystallography, X-Ray
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Fluorescence Resonance Energy Transfer
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Glycylglycine / chemistry
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Glycylglycine / pharmacology
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Minocycline / analogs & derivatives*
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Minocycline / chemistry
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Minocycline / pharmacology
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Models, Molecular
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Protein Biosynthesis / drug effects
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RNA, Bacterial / chemistry
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RNA, Bacterial / genetics
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RNA, Bacterial / metabolism
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RNA, Transfer / chemistry
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RNA, Transfer / genetics
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RNA, Transfer / metabolism
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Ribosomes / chemistry
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Ribosomes / drug effects
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Ribosomes / metabolism
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Static Electricity
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Structure-Activity Relationship
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Thermus thermophilus / drug effects
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Thermus thermophilus / genetics
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Thermus thermophilus / metabolism
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Tigecycline
Substances
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Anti-Bacterial Agents
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RNA, Bacterial
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Glycylglycine
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Tigecycline
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RNA, Transfer
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Minocycline
Associated data
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PDB/4G5K
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PDB/4G5L
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PDB/4G5T
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PDB/4G5U