Evidence map›Paper›PMID 20860410›Full record

ArticleBiochemistry2010

Long-range interaction networks in the function and fidelity of poliovirus RNA-dependent RNA polymerase studied by nuclear magnetic resonance.

Xiaorong Yang, Jesse L Welch, Jamie J Arnold, David D Boehr

Abstract read
In one paragraph

Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

33 citing papers in PubMed, 44 citations in OpenAlex.

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  11. Fidelity Variants and RNA Quasispecies.Current topics in microbiology and immunology · 2016
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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

4 authors at 2 institutions in 2 countries.

Xiaorong YangDepartment of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.
Jesse L Welch
Jamie J Arnold
David D Boehr
Pennsylvania State University · USCancer Institute (WIA) · IN

Funding

RNA DEPENDENT RNA POLYMERASE MECHANISMR01AI045818 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ARNOLD, JAMIE JON, CAMERON, CRAIG E. · 1999 to 2025
$7.5M
NIAID NIH HHS AI45818NIAID NIH HHS R01 AI045818
6 · The paper itself

Abstract

The fidelity of the poliovirus RNA-dependent RNA polymerase (3D(pol)) plays a direct role in the genomic evolution and pathogenesis of the virus. A single site mutation (Gly64Ser) that is remote from the catalytic center results in a higher fidelity polymerase. NMR studies with [methyl-(13)C]methionine-labeled protein were used to compare the solution structure and dynamics of wild-type and Gly64Ser 3D(pol). The chemical shifts for the Met6 resonance were significantly different between wild-type and Gly64Ser 3D(pol) when bound in ternary complexes with RNA and incorrect, but not with correct, nucleotide, suggesting that the Gly64Ser mutation induces structural changes in the N-terminal β-strand when the enzyme is bound to incorrect but not correct nucleotide. We also observe changes in the transverse relaxation times for methionines near regions important for nucleotide and RNA binding and catalysis. Our strategy to assign the [methyl-(13)C]methionine resonances involved separately mutating each of the 17 methionines. Several substitutions produced additional resonances for both Met6 and Met187, a reporter for RNA binding, and conformational changes in the highly conserved motif B loop, even though these methionines are greater than 20 Å apart. The results for Gly64Ser and the other mutants are intriguing considering that they can result in structural and/or dynamic changes to methionines distant from the site of mutation. We propose that there is a long-distance network operating throughout 3D(pol) that coordinates ligand binding, conformational changes, and catalysis. Mutation of Gly64 results in structural and/or dynamic changes to the network that may affect polymerase fidelity.

Indexed as

Magnetic Resonance SpectroscopyMutation, MissenseCatalysisLigandsMethionineNucleotidesPoliovirusProtein BindingProtein ConformationRNA-Dependent RNA PolymeraseLigandsMethionineNucleotidesRNA-Dependent RNA Polymerase

Identifiers

PMID20860410
PMCPMC2989882
OpenAlexW2000031071

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.