Evidence map›Paper›PMID 26028538›Full record

ArticleMolecular cell2015

Distinct tRNA Accommodation Intermediates Observed on the Ribosome with the Antibiotics Hygromycin A and A201A.

Yury S Polikanov, Agata L Starosta, Manuel F Juette, Roger B Altman, Daniel S Terry, Wanli Lu, Benjamin J Burnett, George Dinos, Kevin A Reynolds, Scott C Blanchard and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 93 citations in OpenAlex.

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1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 3 countries.

Yury S PolikanovDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Agata L StarostaGene Center and Department for Biochemistry, University of Munich, Feodor-Lynenstr. 25, 81377 Munich, Germany.
Manuel F JuetteDepartment of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY 10065, USA.
Roger B AltmanDepartment of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY 10065, USA.
Daniel S TerryDepartment of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY 10065, USA.
Wanli LuDepartment of Chemistry, Portland State University, Portland, OR 97207, USA.
Benjamin J BurnettDepartment of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY 10065, USA.
George DinosDepartment of Biochemistry, School of Medicine, University of Patras, 26500 Patras, Greece.
Kevin A ReynoldsDepartment of Chemistry, Portland State University, Portland, OR 97207, USA.
Scott C BlanchardDepartment of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY 10065, USA; Tri-Institutional Training Program in Chemical Biology, New York, NY 10065, USA. Electronic address: scb2005@med.cornell.edu.
Thomas A SteitzDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: thomas.steitz@yale.edu.
Daniel N WilsonGene Center and Department for Biochemistry, University of Munich, Feodor-Lynenstr. 25, 81377 Munich, Germany; Center for integrated Protein Science Munich (CiPSM), University of Munich, Feodor-Lynenstr. 25, 81377 Munich, Germany. Electronic address: wilson@lmb.uni-muenchen.de.
Cornell University · USPortland State University · USCenter for Integrated Protein Science Munich · DEHoward Hughes Medical Institute · USUniversity of Patras · GRYale University · US

Funding

X-RAY ANALYSIS OF PROTEIN STRUCTURE AND FUNCTIONP01GM022778 · NIGMS · YALE UNIVERSITY · PI BREAKER, RONALD R · 1985 to 2019
$26.1M
Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
Imaging Protein Synthesis on the Ribosome using Single-Molecule FRETR01GM079238 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI BLANCHARD, SCOTT C · 2006 to 2023
$7.0M
Next-generation Fluorescent Probes for Biological ResearchR01GM098859 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI BLANCHARD, SCOTT C · 2012 to 2019
$2.9M
Hygromycin A: Activity, Biosynthesis, Export, Resistance and RegulationR01GM095737 · NIGMS · PORTLAND STATE UNIVERSITY · PI REYNOLDS, KEVIN A · 2011 to 2014
$1.2M
NIGMS NIH HHS GM022778NIGMS NIH HHS GM079238NIGMS NIH HHS GM095737NIGMS NIH HHS GM098859NIGMS NIH HHS P01 GM022778NIGMS NIH HHS P41 GM103403NIGMS NIH HHS R01 GM079238NIGMS NIH HHS R01 GM095737NIGMS NIH HHS R01 GM098859
6 · The paper itself

Abstract

The increase in multi-drug-resistant bacteria is limiting the effectiveness of currently approved antibiotics, leading to a renewed interest in antibiotics with distinct chemical scaffolds. We have solved the structures of the Thermus thermophilus 70S ribosome with A-, P-, and E-site tRNAs bound and in complex with either the aminocyclitol-containing antibiotic hygromycin A (HygA) or the nucleoside antibiotic A201A. Both antibiotics bind at the peptidyl transferase center and sterically occlude the CCA-end of the A-tRNA from entering the A site of the peptidyl transferase center. Single-molecule Förster resonance energy transfer (smFRET) experiments reveal that HygA and A201A specifically interfere with full accommodation of the A-tRNA, leading to the presence of tRNA accommodation intermediates and thereby inhibiting peptide bond formation. Thus, our results provide not only insight into the mechanism of action of HygA and A201A, but also into the fundamental process of tRNA accommodation during protein synthesis.

Indexed as

AminoglycosidesAnti-Bacterial AgentsCinnamatesCrystallography, X-RayDisk Diffusion Antimicrobial TestsDrug Resistance, BacterialEscherichia coliHydrogen BondingHygromycin BModels, MolecularProtein ConformationRibosome Subunits, Large, BacterialRibosome Subunits, Small, BacterialRNA, TransferThermus thermophilusA 201AAminoglycosidesAnti-Bacterial AgentsCinnamateshygromycin AHygromycin BRNA, Transfer

Identifiers

PMID26028538
PMCPMC4458074
OpenAlexW2119097418

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.