Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 113, Issue 27, Page 7527-7532, Year 2016
Publish date	Jul 5, 2016
Authors	Stefan Arenz / Manuel F Juette / Michael Graf / Fabian Nguyen / Paul Huter / Yury S Polikanov / Scott C Blanchard / Daniel N Wilson /
PubMed Abstract	The ribosome is one of the major targets for therapeutic antibiotics; however, the rise in multidrug resistance is a growing threat to the utility of our current arsenal. The orthosomycin antibiotics ...The ribosome is one of the major targets for therapeutic antibiotics; however, the rise in multidrug resistance is a growing threat to the utility of our current arsenal. The orthosomycin antibiotics evernimicin (EVN) and avilamycin (AVI) target the ribosome and do not display cross-resistance with any other classes of antibiotics, suggesting that they bind to a unique site on the ribosome and may therefore represent an avenue for development of new antimicrobial agents. Here we present cryo-EM structures of EVN and AVI in complex with the Escherichia coli ribosome at 3.6- to 3.9-Å resolution. The structures reveal that EVN and AVI bind to a single site on the large subunit that is distinct from other known antibiotic binding sites on the ribosome. Both antibiotics adopt an extended conformation spanning the minor grooves of helices 89 and 91 of the 23S rRNA and interacting with arginine residues of ribosomal protein L16. This binding site overlaps with the elbow region of A-site bound tRNA. Consistent with this finding, single-molecule FRET (smFRET) experiments show that both antibiotics interfere with late steps in the accommodation process, wherein aminoacyl-tRNA enters the peptidyltransferase center of the large ribosomal subunit. These data provide a structural and mechanistic rationale for how these antibiotics inhibit the elongation phase of protein synthesis.
External links	Proc Natl Acad Sci U S A / PubMed:27330110 / PubMed Central
Methods	EM (single particle)
Resolution	3.6 - 3.9 Å
Structure data	8237 5kcr EMDB-8237, PDB-5kcr: Cryo-EM structure of the Escherichia coli 70S ribosome in complex with antibiotic Avilamycin C, mRNA and P-site tRNA at 3.6A resolution Method: EM (single particle) / Resolution: 3.6 Å 8238 5kcs EMDB-8238, PDB-5kcs: Cryo-EM structure of the Escherichia coli 70S ribosome in complex with antibiotic Evernimycin, mRNA, TetM and P-site tRNA at 3.9A resolution Method: EM (single particle) / Resolution: 3.9 Å
Chemicals	ChemComp-6UQ: (2R,3S,4R,6S)-4-hydroxy-6-{[(2R,3aR,4R,4'R,5'S,6S,6'R,7aR)-4'-hydroxy-6-{[(2S,3R,4R,5S,6R)-3-hydroxy-2-{[(2R,3S,4S,5S,6S)-4-hydroxy-6-({(2R,3aS,3a'R,6S,6'R,7R,7'R,7aR,7a'R)-7'-hydroxy-7'-[(1S)-1-hydroxyethyl]-6'-methyl-7-[(2-methylpropanoyl)oxy]octahydro-4H-2,4'-spirobi[[1,3]dioxolo[4,5-c]pyran]-6-yl}oxy)-5-methoxy-2-(methoxymethyl)tetrahydro-2H-pyran-3-yl]oxy}-5-methoxy-6-methyltetrahydro-2H-pyran-4-yl]oxy}-4,6',7a-trimethyloctahydro-4H-spiro[1,3-dioxolo[4,5-c]pyran-2,2'-pyran]-5'-yl]oxy}-2-methyltetrahydro-2H-pyran-3-yl 3,5-dichloro-4-hydroxy-2-methoxy-6-methylbenzoate (non-preferred name) ChemComp-ZN: Unknown entry ChemComp-EVN: (2R,3R,4R,6S)-6-{[(2R,3aR,4R,4'R,5'S,6S,6'R,7S,7aR)-6-{[(2S,3R,4R,5S,6R)-2-{[(2R,3S,4S,5S,6S)-6-({(2R,3aS,3a'R,6S,7R,7'
Source	Escherichia coli (E. coli) escherichia coli (strain k12) (bacteria) synthetic (others) synthetic construct (others) enterococcus faecalis (bacteria)
Keywords	RIBOSOME / Avilamycin / evernimycin / antibiotic / antimicrobial / cryo-EM / smFRET / rRNA / L16 / resistance / translation