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Yorodumi- PDB-5kcr: Cryo-EM structure of the Escherichia coli 70S ribosome in complex... -
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-Basic information
Entry | Database: PDB / ID: 5kcr | |||||||||||||||||||||
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Title | Cryo-EM structure of the Escherichia coli 70S ribosome in complex with antibiotic Avilamycin C, mRNA and P-site tRNA at 3.6A resolution | |||||||||||||||||||||
Components |
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Keywords | RIBOSOME / Avilamycin / evernimycin / antibiotic / antimicrobial / cryo-EM / smFRET / rRNA / L16 / resistance / translation | |||||||||||||||||||||
Function / homology | Function and homology information stringent response / ornithine decarboxylase inhibitor activity / transcription antitermination factor activity, RNA binding / misfolded RNA binding / Group I intron splicing / RNA folding / transcriptional attenuation / endoribonuclease inhibitor activity / RNA-binding transcription regulator activity / positive regulation of ribosome biogenesis ...stringent response / ornithine decarboxylase inhibitor activity / transcription antitermination factor activity, RNA binding / misfolded RNA binding / Group I intron splicing / RNA folding / transcriptional attenuation / endoribonuclease inhibitor activity / RNA-binding transcription regulator activity / positive regulation of ribosome biogenesis / negative regulation of cytoplasmic translation / four-way junction DNA binding / translational termination / DnaA-L2 complex / translation repressor activity / negative regulation of DNA-templated DNA replication initiation / negative regulation of translational initiation / regulation of mRNA stability / mRNA regulatory element binding translation repressor activity / ribosome assembly / assembly of large subunit precursor of preribosome / positive regulation of RNA splicing / transcription elongation factor complex / cytosolic ribosome assembly / regulation of DNA-templated transcription elongation / DNA endonuclease activity / response to reactive oxygen species / transcription antitermination / regulation of cell growth / DNA-templated transcription termination / maintenance of translational fidelity / response to radiation / mRNA 5'-UTR binding / ribosomal small subunit biogenesis / small ribosomal subunit rRNA binding / large ribosomal subunit / ribosome biogenesis / ribosome binding / regulation of translation / ribosomal small subunit assembly / small ribosomal subunit / 5S rRNA binding / large ribosomal subunit rRNA binding / transferase activity / cytosolic small ribosomal subunit / ribosomal large subunit assembly / cytoplasmic translation / cytosolic large ribosomal subunit / tRNA binding / molecular adaptor activity / negative regulation of translation / rRNA binding / ribosome / structural constituent of ribosome / translation / response to antibiotic / negative regulation of DNA-templated transcription / mRNA binding / DNA binding / RNA binding / zinc ion binding / membrane / cytosol / cytoplasm Similarity search - Function | |||||||||||||||||||||
Biological species | Escherichia coli (E. coli) Synthetic (others) | |||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||||||||||||||
Authors | Arenz, S. / Juette, M.F. / Graf, M. / Nguyen, F. / Huter, P. / Polikanov, Y.S. / Blanchard, S.C. / Wilson, D.N. | |||||||||||||||||||||
Funding support | United States, Germany, 6items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2016 Title: Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome. Authors: Stefan Arenz / Manuel F Juette / Michael Graf / Fabian Nguyen / Paul Huter / Yury S Polikanov / Scott C Blanchard / Daniel N Wilson / 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. | |||||||||||||||||||||
History |
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-Structure visualization
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Structure viewer | Molecule: MolmilJmol/JSmol |
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PDBx/mmCIF format | 5kcr.cif.gz | 3.2 MB | Display | PDBx/mmCIF format |
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PDB format | pdb5kcr.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 5kcr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5kcr_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 5kcr_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 5kcr_validation.xml.gz | 201.6 KB | Display | |
Data in CIF | 5kcr_validation.cif.gz | 350.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kc/5kcr ftp://data.pdbj.org/pub/pdb/validation_reports/kc/5kcr | HTTPS FTP |
-Related structure data
Related structure data | 8237MC 8238C 5kcsC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
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-Components
-RNA chain , 5 types, 5 molecules 1A1B1a1v1x
#1: RNA chain | Mass: 941813.562 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: GenBank: 802133627 |
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#2: RNA chain | Mass: 38790.090 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: GenBank: 991970073 |
#33: RNA chain | Mass: 498725.406 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: GenBank: 731469900 |
#54: RNA chain | Mass: 2832.727 Da / Num. of mol.: 1 / Source method: obtained synthetically / Details: Synthetic mRNA / Source: (synth.) Synthetic (others) |
#55: RNA chain | Mass: 28094.645 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: GenBank: 1016298593 |
+50S ribosomal protein ... , 30 types, 30 molecules 1D1E1F1G1H1I1J1K1N1O1P1Q1R1S1T1U1V1W1X1Y1Z101112131516171819
-30S ribosomal protein ... , 20 types, 20 molecules 1b1c1d1e1f1g1h1i1j1k1l1m1n1o1p1q1r1s1t1u
#34: Protein | Mass: 26781.670 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0A7V0 |
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#35: Protein | Mass: 26031.316 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0A7V3 |
#36: Protein | Mass: 23514.199 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0A7V8 |
#37: Protein | Mass: 17629.398 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0A7W1 |
#38: Protein | Mass: 15727.512 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P02358 |
#39: Protein | Mass: 20055.156 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P02359 |
#40: Protein | Mass: 14146.557 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0A7W7 |
#41: Protein | Mass: 14886.270 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0A7X3 |
#42: Protein | Mass: 11755.597 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0A7R5 |
#43: Protein | Mass: 13870.975 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0A7R9 |
#44: Protein | Mass: 13768.157 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0A7S3 |
#45: Protein | Mass: 13128.467 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0A7S9 |
#46: Protein | Mass: 11606.560 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0AG59 |
#47: Protein | Mass: 10290.816 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0ADZ4 |
#48: Protein | Mass: 9207.572 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0A7T3 |
#49: Protein | Mass: 9724.491 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0AG63 |
#50: Protein | Mass: 9005.472 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0A7T7 |
#51: Protein | Mass: 10455.355 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0A7U3 |
#52: Protein | Mass: 9708.464 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P0A7U7 |
#53: Protein | Mass: 8524.039 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Escherichia coli (strain K12) (bacteria) / Strain: K12 / References: UniProt: P68679 |
-Non-polymers , 2 types, 2 molecules
#56: Chemical | ChemComp-6UQ / ( |
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