Evidence map›Paper›PMID 15479787›Full record

ArticleNucleic acids research2004

Electrostatic analysis of the hepatitis C virus NS3 helicase reveals both active and allosteric site locations.

David N Frick, Ryan S Rypma, Angela M I Lam, Christopher M Frenz

Open access · bronzeAbstract read
In one paragraph

Article in Nucleic acids research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

23 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Conserved motifs in the flavivirus NS3 RNA helicase enzyme.Wiley interdisciplinary reviews. RNA · 2022
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Tracing entire operation cycles of molecular motor hepatitis C virus helicase in structurally resolved dynamical simulations.Proceedings of the National Academy of Sciences of the United States of America · 2010
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
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 1 institution in 1 country.

David N FrickDepartment of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA. David_Frick@NYMC.edu
Ryan S Rypma
Angela M I Lam
Christopher M Frenz
New York Medical College · US

Funding

Enzymatic Differences Among Hepatitis C Virus GenotypesR01AI052395 · NIAID · NEW YORK MEDICAL COLLEGE · PI FRICK, DAVID N · 2003 to 2007
$1.5M
NIAID NIH HHS AI052395NIAID NIH HHS R01 AI052395
6 · The paper itself

Abstract

Multi-conformation continuum electrostatics (MCCE) was used to analyze various structures of the NS3 RNA helicase from the hepatitis C virus in order to determine the ionization state of amino acid side chains and their pK(a)s. In MCCE analyses of HCV helicase structures that lacked ligands, several active site residues were identified to have perturbed pK(a)s in both the nucleic acid binding site and in the distant ATP-binding site, which regulates helicase movement. In all HCV helicase structures, Glu493 was unusually basic and His369 was abnormally acidic. Both these residues are part of the HCV helicase nucleic acid binding site, and their roles were analyzed by examining the pH profiles of site-directed mutants. Data support the accuracy of MCCE predicted pK(a) values, and reveal that Glu493 is critical for low pH enzyme activation. Several key residues, which were previously shown to be involved in helicase-catalyzed ATP hydrolysis, were also identified to have perturbed pK(a)s including Lys210 in the Walker-A motif and the DExD/H-box motif residues Asp290 and His293. When DNA was present in the structure, the calculated pK(a)s shifted for both Lys210 and Asp290, demonstrating how DNA binding might lead to electrostatic changes that stimulate ATP hydrolysis.

Indexed as

Allosteric SiteBinding SitesDEAD-box RNA HelicasesHydrogen-Ion ConcentrationMutagenesis, Site-DirectedNucleoside-TriphosphataseProtein ConformationRNA HelicasesSerine EndopeptidasesStatic ElectricityViral Nonstructural ProteinsViral ProteasesDEAD-box RNA HelicasesNS3 protein, hepatitis C virusNucleoside-TriphosphataseRNA HelicasesSerine EndopeptidasesViral Nonstructural ProteinsViral Proteases

Identifiers

PMID15479787
PMCPMC524300
OpenAlexW2164045715

What OpenQuestion holds

Textmetadata
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.