Evidence map›Paper›PMID 12485993›Full record

ArticleThe EMBO journal2002

Physiological calcium concentrations regulate calmodulin binding and catalysis of adenylyl cyclase exotoxins.

Yuequan Shen, Young-Sam Lee, Sandriyana Soelaiman, Pamela Bergson, Dan Lu, Alice Chen, Kathy Beckingham, Zenon Grabarek, Milan Mrksich, Wei-Jen Tang

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
2.3field-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

46 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
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  5. Review
  6. Article
  7. Calmodulin as CaInternational journal of molecular sciences · 2021
    Article
  8. AnalyzingFrontiers in molecular biosciences · 2020
    Article
  9. Review
  10. Physical exertion exacerbates decline in the musculature of an animal model of Duchenne muscular dystrophy.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  11. Article
  12. Article
  13. Article
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  16. Review
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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

10 authors at 1 institution in 1 country.

Yuequan ShenBen-May Institute for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Young-Sam Lee
Sandriyana Soelaiman
Pamela Bergson
Dan Lu
Alice Chen
Kathy Beckingham
Zenon Grabarek
Milan Mrksich
Wei-Jen Tang
May Institute · US

Funding

X-ray Crystallographic Investigation of Smooth Muscle RegulationP01AR041637 · NIAMS · BOSTON BIOMEDICAL RESEARCH INSTITUTE · PI TAO, TERENCE · 1992 to 2007
$15.1M
CALMODULIN REGULATION OF ANTHRAX AND ADENYLYL CYCLASESR01GM062548 · NIGMS · UNIVERSITY OF CHICAGO · PI TANG, WEI-JEN · 2001 to 2009
$2.6M
REGULATION OF MAMMALIAN MEMBRANE-BOUND ADENYLYL CYCLASER01GM053459 · NIGMS · UNIVERSITY OF CHICAGO · PI TANG, WEI-JEN · 1996 to 2003
$1.0M
NIAMS NIH HHS AR41637NIAMS NIH HHS P01 AR041637NIGMS NIH HHS GM53459NIGMS NIH HHS GM62548NIGMS NIH HHS R01 GM062548
6 · The paper itself

Abstract

Edema factor (EF) and CyaA are calmodulin (CaM)-activated adenylyl cyclase exotoxins involved in the pathogenesis of anthrax and whooping cough, respectively. Using spectroscopic, enzyme kinetic and surface plasmon resonance spectroscopy analyses, we show that low Ca(2+) concentrations increase the affinity of CaM for EF and CyaA causing their activation, but higher Ca(2+) concentrations directly inhibit catalysis. Both events occur in a physiologically relevant range of Ca(2+) concentrations. Despite the similarity in Ca(2+) sensitivity, EF and CyaA have substantial differences in CaM binding and activation. CyaA has 100-fold higher affinity for CaM than EF. CaM has N- and C-terminal globular domains, each binding two Ca(2+) ions. CyaA can be fully activated by CaM mutants with one defective C-terminal Ca(2+)-binding site or by either terminal domain of CaM while EF cannot. EF consists of a catalytic core and a helical domain, and both are required for CaM activation of EF. Mutations that decrease the interaction of the helical domain with the catalytic core create an enzyme with higher sensitivity to Ca(2+)-CaM activation. However, CyaA is fully activated by CaM without the domain corresponding to the helical domain of EF.

Indexed as

Adenylyl CyclasesBinding SitesCalciumCalmodulinCatalysisDose-Response Relationship, DrugEnzyme ActivationEscherichia coliExotoxinsMagnesiumModels, MolecularMutationPlasmidsProtein BindingProtein Structure, TertiaryRecombinant ProteinsAdenylyl CyclasesCalciumCalmodulinedema factorExotoxinsMagnesiumRecombinant ProteinsViper VenomsNon-programmatic

Identifiers

PMID12485993
PMCPMC139101
OpenAlexW2023062743

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.