Evidence map›Paper›PMID 24079850›Full record

ArticleBiochemistry2013

Transient-state kinetics of apurinic/apyrimidinic (AP) endonuclease 1 acting on an authentic AP site and commonly used substrate analogs: the effect of diverse metal ions and base mismatches.

Kelly M Schermerhorn, Sarah Delaney

Abstract read
In one paragraph

Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

32 citing papers in PubMed.

  1. Article
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  8. PromotersRSC chemical biology · 2023
    Article
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  18. HumanJournal of the American Chemical Society · 2019
    Article
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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

2 authors.

Kelly M SchermerhornDepartment of Chemistry, Brown University , 324 Brook Street, Providence, Rhode Island 02912, United States.
Sarah Delaney

Funding

Inflammation as a Mediator of Dynamic DNA MutationsR01ES019296 · NIEHS · BROWN UNIVERSITY · PI DELANEY, SARAH · 2010 to 2014
$2.2M
NIEHS NIH HHS R01 ES019296
6 · The paper itself

Abstract

Apurinic/apyrimidinic endonuclease 1 (APE1) is an Mg²⁺-dependent enzyme responsible for incising the DNA backbone 5' to an apurinic/apyrimidinic (AP) site. Here, we use rapid quench flow (RQF) techniques to provide a comprehensive kinetic analysis of the strand-incision activity (k(chemistry)) of APE1 acting on an authentic AP site along with two widely used analogs, a reduced AP site and a tetrahydrofuran (THF) site. In the presence of biologically relevant Mg²⁺, APE1 incises all three substrates at a rate faster than the resolution of the RQF, ≥700 s⁻¹. To obtain quantitative values of k(chemistry) and to facilitate a comparison of the authentic substrate versus the substrate analogs, we replaced Mg²⁺ with Mn²⁺ or Ni²⁺ or introduced a mismatch 5' to the lesion site. Both strategies were sufficient to slow k(chemistry) and resulted in rates within the resolution of the RQF. In all cases where quantitative rates were obtained, k(chemistry) for the reduced AP site is indistinguishable from the authentic AP site. Notably, there is a small decrease, ~1.5-fold, in k(chemistry) for the THF site relative to the authentic AP site. These results highlight a role in strand incision for the C1' oxygen of the AP site and warrant consideration when designing experiments using substrate analogs.

Indexed as

Base Pair MismatchModels, MolecularBinding SitesChelating AgentsDNADNA-(Apurinic or Apyrimidinic Site) LyaseHumansKineticsLigandsMagnesiumManganeseNickelNucleotide MotifsProtein StabilityRecombinant ProteinsSubstrate SpecificityAPEX1 protein, humanChelating AgentsDNADNA-(Apurinic or Apyrimidinic Site) LyaseLigandsMagnesiumManganeseNickelRecombinant Proteins

Identifiers

PMID24079850
PMCPMC3859843

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Registered trials

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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.