EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 113, Issue 27, Page 7527-7532, Year 2016
掲載日	2016年7月5日
著者	Stefan Arenz / Manuel F Juette / Michael Graf / Fabian Nguyen / Paul Huter / Yury S Polikanov / Scott C Blanchard / Daniel N Wilson /
PubMed 要旨	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.
リンク	Proc Natl Acad Sci U S A / PubMed:27330110 / PubMed Central
手法	EM (単粒子)
解像度	3.6 - 3.9 Å
構造データ	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 手法: EM (単粒子) / 解像度: 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 手法: EM (単粒子) / 解像度: 3.9 Å
化合物	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'
由来	Escherichia coli (大腸菌) escherichia coli (strain k12) (大腸菌) synthetic (人工物) synthetic construct (人工物) enterococcus faecalis (乳酸球菌)
キーワード	RIBOSOME (リボソーム) / Avilamycin / evernimycin / antibiotic (抗生物質) / antimicrobial / cryo-EM (低温電子顕微鏡法) / smFRET / rRNA (リボソームRNA) / L16 / resistance / translation (翻訳 (生物学))