Evidence map›Paper›PMID 30418757›Full record

ArticleBiochemistry2019

Inhibiting APOBEC3 Activity with Single-Stranded DNA Containing 2'-Deoxyzebularine Analogues.

Maksim V Kvach, Fareeda M Barzak, Stefan Harjes, Henry A M Schares, Geoffrey B Jameson, Alex M Ayoub, Ramkumar Moorthy, Hideki Aihara, Reuben S Harris, Vyacheslav V Filichev and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Biochemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

38 citing papers in PubMed, 48 citations in OpenAlex.

  1. Review
  2. Review
  3. Deaminase Modulation Driving a New Era in Drug Development.International journal of molecular sciences · 2025
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Development of Allosteric Small Molecule APOBEC3B Inhibitors frombioRxiv : the preprint server for biology · 2024
    Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Clinical Implications of APOBEC3-Mediated Mutagenesis in Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Review
  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

12 authors at 3 institutions in 2 countries.

Maksim V KvachInstitute of Fundamental Sciences , Massey University , Private Bag 11 222, Palmerston North 4442 , New Zealand.
Fareeda M BarzakInstitute of Fundamental Sciences , Massey University , Private Bag 11 222, Palmerston North 4442 , New Zealand.
Stefan HarjesInstitute of Fundamental Sciences , Massey University , Private Bag 11 222, Palmerston North 4442 , New Zealand.
Henry A M Schares
Geoffrey B JamesonInstitute of Fundamental Sciences , Massey University , Private Bag 11 222, Palmerston North 4442 , New Zealand.
Alex M Ayoub
Ramkumar Moorthy
Reuben S HarrisHoward Hughes Medical Institute , University of Minnesota , Minneapolis , Minnesota 55455 , United States.
Vyacheslav V FilichevInstitute of Fundamental Sciences , Massey University , Private Bag 11 222, Palmerston North 4442 , New Zealand.ORCID 0000-0002-7383-3025
Elena HarjesInstitute of Fundamental Sciences , Massey University , Private Bag 11 222, Palmerston North 4442 , New Zealand.ORCID 0000-0002-3643-9432
University of Minnesota · USMassey University · NZMaurice Wilkins Centre · NZ

Funding

Structural studies of viral replication and invasionR35GM118047 · NIGMS · UNIVERSITY OF MINNESOTA · PI Hideki Aihara · 2016 to 2026
$6.3M
APOBEC3 STRUCTURAL STUDIESR01GM118000 · NIGMS · UNIVERSITY OF MINNESOTA · PI AIHARA, HIDEKI, HARRIS, REUBEN S · 2016 to 2019
$2.2M
Chemical Interrogation of Human DNA Cytosine DeaminasesR01GM110129 · NIGMS · UNIVERSITY OF MINNESOTA · PI HARKI, DANIEL A · 2015 to 2019
$1.8M
NIGMS NIH HHS R01 GM110129NIGMS NIH HHS R01 GM118000NIGMS NIH HHS R35 GM118047Worldwide Cancer Research 16-1197
6 · The paper itself

Abstract

APOBEC3 enzymes form part of the innate immune system by deaminating cytosine to uracil in single-stranded DNA (ssDNA) and thereby preventing the spread of pathogenic genetic information. However, APOBEC mutagenesis is also exploited by viruses and cancer cells to increase rates of evolution, escape adaptive immune responses, and resist drugs. This raises the possibility of APOBEC3 inhibition as a strategy for augmenting existing antiviral and anticancer therapies. Here we show that, upon incorporation into short ssDNAs, the cytidine nucleoside analogue 2'-deoxyzebularine (dZ) becomes capable of inhibiting the catalytic activity of selected APOBEC variants derived from APOBEC3A, APOBEC3B, and APOBEC3G, supporting a mechanism in which ssDNA delivers dZ to the active site. Multiple experimental approaches, including isothermal titration calorimetry, fluorescence polarization, protein thermal shift, and nuclear magnetic resonance spectroscopy assays, demonstrate nanomolar dissociation constants and low micromolar inhibition constants. These dZ-containing ssDNAs constitute the first substrate-like APOBEC3 inhibitors and, together, comprise a platform for developing nucleic acid-based inhibitors with cellular activity.

Indexed as

APOBEC-3G DeaminaseCytidineCytidine DeaminaseDNA, Single-StrandedEnzyme InhibitorsHumansMinor Histocompatibility AntigensProteins2'-deoxyzebularineAPOBEC3A protein, humanAPOBEC3B protein, humanAPOBEC-3G DeaminaseAPOBEC3G protein, humanCytidineCytidine DeaminaseDNA, Single-StrandedEnzyme InhibitorsMinor Histocompatibility AntigensProteins

Identifiers

PMID30418757
PMCPMC6365909
OpenAlexW2901169643

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.