Evidence map›Paper›PMID 23353829›Full record

ArticleJournal of molecular biology2013

Allosteric inhibition of a zinc-sensing transcriptional repressor: insights into the arsenic repressor (ArsR) family.

Gregory C Campanello, Zhen Ma, Nicholas E Grossoehme, Alfredo J Guerra, Brian P Ward, Richard D Dimarchi, Yuzhen Ye, Charles E Dann, David P Giedroc

Abstract 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 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.5field-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

23 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
  2. Article
  3. Structural and functional mapping ofComputational and structural biotechnology journal · 2023
    Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Allosteric histidine switch for regulation of intracellular zinc(II) fluctuation.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  13. Article
  14. Review
  15. Entropy redistribution controls allostery in a metalloregulatory protein.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  16. Article
  17. Article
  18. Article
  19. A moonlighting function of Mycobacterium smegmatis Ku in zinc homeostasis?Protein science : a publication of the Protein Society · 2015
    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

9 authors at 2 institutions in 1 country.

Gregory C CampanelloDepartment of Chemistry, Indiana University, Bloomington, IN 47405-7102, USA.
Zhen Ma
Nicholas E Grossoehme
Alfredo J Guerra
Brian P Ward
Richard D Dimarchi
Yuzhen Ye
Charles E Dann
David P Giedroc
Indiana University Bloomington · USWinthrop University · US

Funding

ZINC COORDINATION AND REGULATION OF ZINC METALLOPROTEINSR01GM042569 · NIGMS · TRUSTEES OF INDIANA UNIVERSITY · PI GIEDROC, DAVID P. · 1996 to 2015
$4.9M
Molecular Analyses of Folate and Antifolate TransportR01GM094472 · NIGMS · TRUSTEES OF INDIANA UNIVERSITY · PI DANN, CHARLES E. · 2010 to 2014
$1.4M
ZINC DOMAIN STRUCTURE AND FUNCTION IN T4 GENE 32 PROTEINR29GM042569 · NIGMS · TEXAS AGRILIFE RESEARCH · PI GIEDROC, DAVID P. · 1991 to 1995
–
NIGMS NIH HHS GM042569NIGMS NIH HHS GM094472NIGMS NIH HHS R01 GM042569NIGMS NIH HHS R01 GM094472
6 · The paper itself

Abstract

The molecular basis of allosteric regulation remains a subject of intense interest. Staphylococcus aureus CzrA is a member of the ubiquitous arsenic repressor (ArsR) family of bacterial homodimeric metal-sensing proteins and has emerged as a model system for understanding allosteric regulation of operator DNA binding by transition metal ions. Using unnatural amino acid substitution and a standard linkage analysis, we show that a His97' NH(ε2)...O=C His67 quaternary structural hydrogen bond is an energetically significant contributor to the magnitude of the allosteric coupling free energy, ∆Gc. A "cavity" introduced just beneath this hydrogen bond in V66A/L68V CzrA results in a significant reduction in regulation by Zn(II) despite adopting a wild-type global structure and Zn(II) binding and DNA binding affinities only minimally affected from wild type. The energetics of Zn(II) binding and heterotropic coupling free energies (∆Hc, -T∆Sc) of the double mutant are also radically altered and suggest that increased internal dynamics leads to poorer allosteric negative regulation in V66A/L68V CzrA. A statistical coupling analysis of 3000 ArsR proteins reveals a sector that links the DNA-binding determinants and the α5 Zn(II)-sensing sites through V66/L68 in CzrA. We propose that distinct regulatory sites uniquely characteristic of individual ArsR proteins result from evolution of distinct connectivities to this sector, each capable of driving the same biological outcome, transcriptional derepression.

Indexed as

Allosteric RegulationAmino Acid SubstitutionBacterial ProteinsBinding, CompetitiveBinding SitesCrystallography, X-RayDNA-Binding ProteinsHydrogen BondingKineticsModels, MolecularMutationProtein BindingProtein MultimerizationProtein Structure, SecondaryProtein Structure, TertiaryRepressor ProteinsBacterial ProteinsCzrA protein, Staphylococcus aureusDNA-Binding ProteinsRepressor ProteinsZinc

Identifiers

PMID23353829
PMCPMC3602352
OpenAlexW2117202122

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.