Evidence map›Paper›PMID 29234087›Full record

ArticleScientific reports2017

Conformational Switch Regulates the DNA Cytosine Deaminase Activity of Human APOBEC3B.

Ke Shi, Özlem Demir, Michael A Carpenter, Jeff Wagner, Kayo Kurahashi, Reuben S Harris, Rommie E Amaro, Hideki Aihara

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

25 citing papers in PubMed, 39 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. Article
  6. Regulatory interactions between APOBEC3B N- and C-terminal domains.bioRxiv : the preprint server for biology · 2024
    Article
  7. Article
  8. Clinical Implications of APOBEC3-Mediated Mutagenesis in Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Interactions of APOBEC3s with DNA and RNA.Current opinion in structural biology · 2021
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

8 authors at 2 institutions in 1 country.

Ke ShiDepartment of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, 55455, USA.
Özlem DemirDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093, USA.
Michael A CarpenterDepartment of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, 55455, USA.
Jeff WagnerDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093, USA.
Kayo KurahashiDepartment of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, 55455, USA.
Reuben S HarrisDepartment of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, 55455, USA.
Rommie E AmaroDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093, USA.ORCID 0000-0002-9275-9553
Hideki AiharaDepartment of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, 55455, USA. aihar001@umn.edu.
University of Minnesota · USUniversity of California San Diego · US

Funding

Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
National Biomedical Computation Resource - Competitive Revision SupplementP41GM103426 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AMARO, ROMMIE E · 2012 to 2019
$14.0M
Structural studies of viral replication and invasionR35GM118047 · NIGMS · UNIVERSITY OF MINNESOTA · PI Hideki Aihara · 2016 to 2026
$6.3M
A Structural Systems Biology Approach to Drug DiscoveryDP2OD007237 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AMARO, ROMMIE E · 2010 to 2015
$2.9M
APOBEC3 STRUCTURAL STUDIESR01GM118000 · NIGMS · UNIVERSITY OF MINNESOTA · PI AIHARA, HIDEKI, HARRIS, REUBEN S · 2016 to 2019
$2.2M
Pixel Array Detector for X-ray CrystallographyS10RR029205 · NCRR · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2010 to 2010
$1.8M
(PQ2) HIV INFECTION, APOBEC UPREGULATION, AND CANCER MUTAGENESISR21CA206309 · NCI · UNIVERSITY OF MINNESOTA · PI HARRIS, REUBEN S · 2016 to 2017
$401k
Howard Hughes Medical InstituteNCI NIH HHS R21 CA206309NCRR NIH HHS S10 RR029205NIGMS NIH HHS P41 GM103403NIGMS NIH HHS P41 GM103426NIGMS NIH HHS R01 GM118000NIGMS NIH HHS R35 GM118047NIH HHS DP2 OD007237
6 · The paper itself

Abstract

The APOBEC3B (A3B) single-stranded DNA (ssDNA) cytosine deaminase has important roles in innate immunity but is also a major endogenous source of mutations in cancer. Previous structural studies showed that the C-terminal catalytic domain of human A3B has a tightly closed active site, and rearrangement of the surrounding loops is required for binding to substrate ssDNA. Here we report structures of the A3B catalytic domain in a new crystal form that show alternative, yet still closed, conformations of active site loops. All-atom molecular dynamics simulations support the dynamic behavior of active site loops and recapitulate the distinct modes of interactions that maintain a closed active site. Replacing segments of A3B loop 1 to mimic the more potent cytoplasmic deaminase APOBEC3A leads to elevated ssDNA deaminase activity, likely by facilitating opening of the active site. These data collectively suggest that conformational equilibrium of the A3B active site loops, skewed toward being closed, controls enzymatic activity by regulating binding to ssDNA substrates.

Indexed as

Amino Acid SequenceCatalytic DomainCytidine DeaminaseDNA, Single-StrandedHumansMinor Histocompatibility AntigensMolecular Dynamics SimulationProtein BindingProtein ConformationSequence AlignmentAPOBEC3B protein, humanCytidine DeaminaseDNA, Single-StrandedMinor Histocompatibility Antigens

Identifiers

PMID29234087
PMCPMC5727031
OpenAlexW2772722150

What OpenQuestion holds

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LicenceCC BY
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.