Evidence map›Paper›PMID 23043620›Full record

ArticleBiochemistry2012

Effect of β,γ-CHF- and β,γ-CHCl-dGTP halogen atom stereochemistry on the transition state of DNA polymerase β.

Keriann Oertell, Yue Wu, Valeria M Zakharova, Boris A Kashemirov, David D Shock, William A Beard, Samuel H Wilson, Charles E McKenna, Myron F Goodman

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

14 citing papers in PubMed, 17 citations in OpenAlex.

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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

9 authors at 3 institutions in 1 country.

Keriann OertellDepartment of Chemistry, University of Southern California, Los Angeles, CA 90089, USA.
Yue Wu
Valeria M Zakharova
Boris A Kashemirov
David D Shock
William A Beard
Samuel H Wilson
Charles E McKenna
Myron F Goodman
University of Southern California · USNational Institute of Environmental Health Sciences · USNational Institutes of Health · US

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
ERROR CORRECTION IN DNA SYNTHESIS--A BIOCHEMICAL STUDYR37GM021422 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GOODMAN, MYRON · 2000 to 2009
$3.5M
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
ERROR CORRECTION IN DNA SYNTHESIS: A BIOCHEMICAL STUDYR01GM021422 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GOODMAN, MYRON · 1985 to 2014
$1.6M
Intramural NIH HHS Z01 ES050158Intramural NIH HHS Z01 ES050159NCI NIH HHS 5-U19-CA105010NCI NIH HHS U19 CA105010NIGMS NIH HHS R01 GM021422NIGMS NIH HHS R01-GM21422NIGMS NIH HHS R37 GM021422
6 · The paper itself

Abstract

Recently, we synthesized the first individual β,γ-CHX-dGTP diastereomers [(R)- or (S)-CHX, where X is F or Cl] and determined their structures in ternary complexes with DNA polymerase β (pol β). We now report stereospecificity by pol β on the mixed β,γ-CHX diastereomer pairs using nuclear magnetic resonance and on the separate diastereomers using transient kinetics. For both the F and Cl diastereomers, the R isomer is favored over the S isomer for G·C correct incorporation, with stereospecificities [(k(pol)/K(d))(R)/(k(pol)/K(d))(S)] of 3.8 and 6.3, respectively, and also for G·T misincorporation, with stereospecificities of 11 and 7.8, respectively. Stereopreference for the (R)-CHF-dGTP diastereomer was abolished for k(pol) but not K(d) with mutant pol β (R183A). These compounds constitute a new class of stereochemical probes for active site interactions involving halogen atoms. As Arg183 is unique in family X pols, the design of CXY deoxyribonucleotide analogues to enhance interaction is a possible strategy for inhibiting BER selectively in cancer cells.

Indexed as

Catalytic DomainDeoxyguanine NucleotidesDNADNA Polymerase betaHalogensHumansKineticsNuclear Magnetic Resonance, BiomolecularPoint MutationStereoisomerismSubstrate SpecificityDeoxyguanine Nucleotidesdeoxyguanosine triphosphateDNADNA Polymerase betaHalogens

Identifiers

PMID23043620
PMCPMC3548995
OpenAlexW2051341054

What OpenQuestion holds

Textmetadata
LicenceTDM
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.