Evidence map›Paper›PMID 26416889›Full record

ArticleThe Journal of biological chemistry2015

Crystal Structure of the DNA Deaminase APOBEC3B Catalytic Domain.

Ke Shi, Michael A Carpenter, Kayo Kurahashi, Reuben S Harris, Hideki Aihara

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
7.2field-weighted citation impact, top 2% 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

69 citing papers in PubMed, 105 citations in OpenAlex.

  1. Article
  2. Article
  3. Regulatory Interactions between APOBEC3B N- and C-Terminal Domains.Journal of chemical information and modeling · 2025
    Article
  4. Article
  5. Regulatory interactions between APOBEC3B N- and C-terminal domains.bioRxiv : the preprint server for biology · 2024
    Article
  6. Article
  7. Development of Allosteric Small Molecule APOBEC3B Inhibitors frombioRxiv : the preprint server for biology · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. The current toolbox for APOBEC drug discovery.Trends in pharmacological sciences · 2022
    Review
  16. Article
  17. Article
  18. Article
  19. Interactions of APOBEC3s with DNA and RNA.Current opinion in structural biology · 2021
    Review
  20. Article

9 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

5 authors at 3 institutions in 3 countries.

Ke ShiDepartment of Biochemistry, Molecular Biology, and Biophysics; Institute for Molecular Virology; Masonic Cancer Center. Electronic address: rsh@umn.edu.
Michael A CarpenterDepartment of Biochemistry, Molecular Biology, and Biophysics; Institute for Molecular Virology; Masonic Cancer Center.
Kayo KurahashiDepartment of Biochemistry, Molecular Biology, and Biophysics; Institute for Molecular Virology; Masonic Cancer Center.
Reuben S HarrisDepartment of Biochemistry, Molecular Biology, and Biophysics; Institute for Molecular Virology; Masonic Cancer Center; Howard Hughes Medical Institute, University of Minnesota, Minneapolis, Minnesota 55455.
Hideki AiharaDepartment of Biochemistry, Molecular Biology, and Biophysics; Institute for Molecular Virology; Masonic Cancer Center.
Institute of Virology of the Slovak Academy of Sciences · SKMasonic Cancer CenterInstitute of Molecular Biology and Biophysics · RU

Funding

Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
Structural Characterization of APOBECS's Atomic interactionsP01GM091743 · NIGMS · UNIVERSITY OF MINNESOTA · PI KOTLER, MOSHE · 2011 to 2015
$10.1M
APOBEC3 Proteins in HIV RestrictionR37AI064046 · NIAID · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI HARRIS, REUBEN S · 2015 to 2024
$4.2M
APOBEC proteins and uracil in retrovirus restrictionR01AI064046 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI HARRIS, REUBEN S · 2005 to 2014
$3.0M
Cellular Nucleotide Metabolism in HIV RestrictionR01GM110734 · NIGMS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI PERRINO, FRED W · 2014 to 2017
$1.5M
Structural studies of DNA resolvases involved in hairpin telomere maintenanceR01GM095558 · NIGMS · UNIVERSITY OF MINNESOTA · PI AIHARA, HIDEKI · 2011 to 2015
$1.4M
Crystallographic studies of retroviral intasome complexesR01GM109770 · NIGMS · UNIVERSITY OF MINNESOTA · PI AIHARA, HIDEKI · 2014 to 2015
$849k
APOBEC3 Proteins in HIV RestrictionR56AI064046 · NIAID · UNIVERSITY OF MINNESOTA · PI HARRIS, REUBEN S · 2010 to 2010
$524k
Howard Hughes Medical InstituteNIAID NIH HHS AI064046NIAID NIH HHS R01 AI064046NIAID NIH HHS R37 AI064046NIAID NIH HHS R56 AI064046NIGMS NIH HHS GM091743NIGMS NIH HHS GM095558NIGMS NIH HHS GM109770NIGMS NIH HHS GM110734NIGMS NIH HHS P01 GM091743NIGMS NIH HHS P41 GM103403NIGMS NIH HHS R01 GM095558NIGMS NIH HHS R01 GM109770NIGMS NIH HHS R01 GM110734
6 · The paper itself

Abstract

Functional and deep sequencing studies have combined to demonstrate the involvement of APOBEC3B in cancer mutagenesis. APOBEC3B is a single-stranded DNA cytosine deaminase that functions normally as a nuclear-localized restriction factor of DNA-based pathogens. However, it is overexpressed in cancer cells and elicits an intrinsic preference for 5'-TC motifs in single-stranded DNA, which is the most frequently mutated dinucleotide in breast, head/neck, lung, bladder, cervical, and several other tumor types. In many cases, APOBEC3B mutagenesis accounts for the majority of both dispersed and clustered (kataegis) cytosine mutations. Here, we report the first structures of the APOBEC3B catalytic domain in multiple crystal forms. These structures reveal a tightly closed active site conformation and suggest that substrate accessibility is regulated by adjacent flexible loops. Residues important for catalysis are identified by mutation analyses, and the results provide insights into the mechanism of target site selection. We also report a nucleotide (dCMP)-bound crystal structure that informs a multistep model for binding single-stranded DNA. Overall, these high resolution crystal structures provide a framework for further mechanistic studies and the development of novel anti-cancer drugs to inhibit this enzyme, dampen tumor evolution, and minimize adverse outcomes such as drug resistance and metastasis.

Indexed as

Catalytic DomainCrystallography, X-RayCytidine DeaminaseEnzyme StabilityHumansMinor Histocompatibility AntigensModels, MolecularProtein ConformationSolubilityAPOBEC3B protein, humanCytidine DeaminaseMinor Histocompatibility AntigensAPOBEC3Bcancercancer mutagenesiscrystal structureDNA binding proteinDNA deaminaseDNA editingDNA repairenzyme mutationMutation

Identifiers

PMID26416889
PMCPMC4653671
OpenAlexW2177028599

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.