Evidence map›Paper›PMID 22959623›Full record

ArticleStructure (London, England : 1993)2012

Structures of dNTP intermediate states during DNA polymerase active site assembly.

Bret D Freudenthal, William A Beard, Samuel H Wilson

Abstract read
In one paragraph

Article in Structure (London, England : 1993), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
–field-weighted citation impact
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

40 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
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  10. Article
  11. Article
  12. Article
  13. Review
  14. Structure and function relationships in mammalian DNA polymerases.Cellular and molecular life sciences : CMLS · 2020
    Review
  15. Structural evidence for an inThe Journal of biological chemistry · 2019
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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

3 authors.

Bret D FreudenthalLaboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Research Triangle Park, NC 27709-2233, USA.
William A Beard
Samuel H Wilson

Funding

Biology of Mammalian Base Excision Repair and HIV-1 ReplicationZIAES050159 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WILSON, SAMUEL H · 2009 to 2022
$29.7M
Mechanisms of Nucleic Acid Enzymes - Pol Beta, HIV-1 Reverse Transcriptase and Mammalian Base Repair EnzymesZIAES050158 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WILSON, SAMUEL H · 2009 to 2022
$17.0M
Mechanistic Analysis of Pol Beta and Cancer-Associated MutantsU19CA105010 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GOODMAN, MYRON · 2004 to 2012
$9.8M
BIOLOGY OF MAMMALIAN BASE EXCISION REPAIRZ01ES050159 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WILSON, SAMUEL H · 1997 to 2008
$4.5M
Nucleic Acid Enzymes--Pol Beta And Base Repair EnzymesZ01ES050158 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WILSON, SAMUEL H · 1997 to 2008
$2.8M
STRUCTURE-ACTIVITY RELATIONSHIPS OF HIV-1 REVERSE TRANSCRIPTASEZ01ES050161 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WILSON, SAMUEL H · 1997 to 2008
$241k
Intramural NIH HHS Z01 ES050158Intramural NIH HHS Z01 ES050159Intramural NIH HHS Z01 ES050161NCI NIH HHS 1U19CA105010NCI NIH HHS U19 CA105010
6 · The paper itself

Abstract

DNA polymerase and substrate conformational changes are essential for high-fidelity DNA synthesis. Structures of DNA polymerase (pol) β in complex with DNA show the enzyme in an "open" conformation. Subsequent to binding the nucleotide, the polymerase "closes" around the nascent base pair with two metals positioned for chemistry. However, structures of substrate/active site intermediates prior to closure are lacking. By destabilizing the closed complex, we determined unique ternary complex structures of pol β with correct and incorrect incoming nucleotides bound to the open conformation. These structures reveal that Watson-Crick hydrogen bonding is assessed upon initial complex formation. Importantly, nucleotide-bound states representing intermediate metal coordination states occur with active site assembly. The correct, but not incorrect, nucleotide maintains Watson-Crick hydrogen bonds during interconversion of these states. These structures indicate that the triphosphate of the incoming nucleotide undergoes rearrangement prior to closure, providing an opportunity to deter misinsertion and increase fidelity.

Indexed as

Catalytic DomainDNA-Directed DNA PolymeraseModels, MolecularDNA-Directed DNA Polymerase

Identifiers

PMID22959623
PMCPMC3496073

What OpenQuestion holds

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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.