6xqd | pdb_00006xqd

Crystal structure of the Thermus thermophilus 70S ribosome in complex with sarecycline, UUC-mRNA, and deacylated P-site tRNA at 2.80A resolution

spinqualitylabelsall models 6xqd, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6xqd is a 20 chain structure with sequence from Thermus thermophilus HB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: 0TD, 2MA, 2MG, 2MU, 4OC, 4SU, 5MC, 5MU, 7MG, M2G, MA6, MG, OMG, PSU, UR3, V7A, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RL2_THET8 One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial (By similarity). Makes several contacts with the 16S rRNA (forming bridge B7b) in the 70S ribosome.[HAMAP-Rule:MF_01320_B] Publication Abstract from PubMed Sarecycline is a new narrow-spectrum tetracycline-class antibiotic approved for the treatment of acne vulgaris. Tetracyclines share a common four-ring naphthacene core and inhibit protein synthesis by interacting with the 70S bacterial ribosome. Sarecycline is distinguished chemically from other tetracyclines because it has a 7-[[methoxy(methyl)amino]methyl] group attached at the C7 position of ring D. To investigate the functional role of this C7 moiety, we determined the X-ray crystal structure of sarecycline bound to the Thermus thermophilus 70S ribosome. Our 2.8-A resolution structure revealed that sarecycline binds at the canonical tetracycline binding site located in the decoding center of the small ribosomal subunit. Importantly, unlike other tetracyclines, the unique C7 extension of sarecycline extends into the messenger RNA (mRNA) channel to form a direct interaction with the A-site codon to possibly interfere with mRNA movement through the channel and/or disrupt A-site codon-anticodon interaction. Based on our biochemical studies, sarecycline appears to be a more potent initiation inhibitor compared to other tetracyclines, possibly due to drug interactions with the mRNA, thereby blocking accommodation of the first aminoacyl transfer RNA (tRNA) into the A site. Overall, our structural and biochemical findings rationalize the role of the unique C7 moiety of sarecycline in antibiotic action. Sarecycline interferes with tRNA accommodation and tethers mRNA to the 70S ribosome.,Batool Z, Lomakin IB, Polikanov YS, Bunick CG Proc Natl Acad Sci U S A. 2020 Aug 25;117(34):20530-20537. doi:, 10.1073/pnas.2008671117. Epub 2020 Aug 12. PMID:32817463 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosome 3D structures

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