Evidence map›Paper›PMID 23938202›Full record

ArticleJournal of molecular biology2013

The local dinucleotide preference of APOBEC3G can be altered from 5'-CC to 5'-TC by a single amino acid substitution.

Anurag Rathore, Michael A Carpenter, Özlem Demir, Terumasa Ikeda, Ming Li, Nadine M Shaban, Emily K Law, Dmitry Anokhin, William L Brown, Rommie E Amaro and 1 more

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
3.3field-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

63 citing papers in PubMed, 99 citations in OpenAlex.

  1. Article
  2. Article
  3. Fitness Landscapes of APOBEC3G Antagonism by HIV-1 Vif proteins.bioRxiv : the preprint server for biology · 2025
    Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Molecular Biology and Diversification of Human Retroviruses.Frontiers in virology (Lausanne, Switzerland) · 2022
    Article
  15. Article
  16. Characterization of an A3G-VifMolecular & cellular proteomics : MCP · 2021
    Article
  17. Article
  18. Review
  19. Article
  20. Article

3 more citing papers are in PubMed but not listed here.

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

11 authors at 3 institutions in 1 country.

Anurag RathoreDepartment of Biochemistry, Molecular Biology and Biophysics, Institute for Molecular Virology, Center for Genome Engineering, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Michael A Carpenter
Özlem Demir
Terumasa Ikeda
Ming Li
Nadine M Shaban
Emily K Law
Dmitry Anokhin
William L Brown
Rommie E Amaro
Reuben S Harris
University of Minnesota · USMasonic Cancer CenterUniversity of California, San Diego · US

Funding

University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR000114 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R · 2012 to 2015
$35.0M
Structural Characterization of APOBECS's Atomic interactionsP01GM091743 · NIGMS · UNIVERSITY OF MINNESOTA · PI MATSUO, HIROSHI · 2011 to 2015
$10.1M
APOBEC proteins and uracil in retrovirus restrictionR01AI064046 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI HARRIS, REUBEN S · 2005 to 2014
$3.0M
A Structural Systems Biology Approach to Drug DiscoveryDP2OD007237 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AMARO, ROMMIE E · 2010 to 2015
$2.9M
Delineating a New Mechanism of Foreign DNA Restriction in Human CellsF32GM095219 · NIGMS · UNIVERSITY OF MINNESOTA · PI CARPENTER, MICHAEL ALLEN · 2010 to 2012
$124k
NCATS NIH HHS UL1 TR000114NIAID NIH HHS R01 AI064046NIGMS NIH HHS F32 GM095219NIGMS NIH HHS P01 GM091743NIH HHS DP2 OD007237NIH HHS DP2-OD007237
6 · The paper itself

Abstract

APOBEC3A and APOBEC3G are DNA cytosine deaminases with biological functions in foreign DNA and retrovirus restriction, respectively. APOBEC3A has an intrinsic preference for cytosine preceded by thymine (5'-TC) in single-stranded DNA substrates, whereas APOBEC3G prefers the target cytosine to be preceded by another cytosine (5'-CC). To determine the amino acids responsible for these strong dinucleotide preferences, we analyzed a series of chimeras in which putative DNA binding loop regions of APOBEC3G were replaced with the corresponding regions from APOBEC3A. Loop 3 replacement enhanced APOBEC3G catalytic activity but did not alter its intrinsic 5'-CC dinucleotide substrate preference. Loop 7 replacement caused APOBEC3G to become APOBEC3A-like and strongly prefer 5'-TC substrates. Simultaneous loop 3/7 replacement resulted in a hyperactive APOBEC3G variant that also preferred 5'-TC dinucleotides. Single amino acid exchanges revealed D317 as a critical determinant of dinucleotide substrate specificity. Multi-copy explicitly solvated all-atom molecular dynamics simulations suggested a model in which D317 acts as a helix-capping residue by constraining the mobility of loop 7, forming a novel binding pocket that favorably accommodates cytosine. All catalytically active APOBEC3G variants, regardless of dinucleotide preference, retained human immunodeficiency virus type 1 restriction activity. These data support a model in which the loop 7 region governs the selection of local dinucleotide substrates for deamination but is unlikely to be part of the higher level targeting mechanisms that direct these enzymes to biological substrates such as human immunodeficiency virus type 1 cDNA.

Indexed as

Amino Acid SubstitutionAPOBEC-3G DeaminaseCytidine DeaminaseHIV-1HumansModels, MolecularMutationProtein ConformationSubstrate SpecificityAPOBEC-3G DeaminaseAPOBEC3G protein, humanCytidine Deaminaseactivation-induced deaminaseAIDAPOBEC3AAPOBEC3GDNA cytosine deaminationHIV-1HIV-1 restrictionhuman immunodeficiency virus type 1local dinucleotide target selectionMDmolecular dynamics

Identifiers

PMID23938202
PMCPMC3812309
OpenAlexW2072976081

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.