Evidence map›Paper›PMID 18211893›Full record

ArticleThe Journal of biological chemistry2008

Calcium binding rigidifies the C2 domain and the intradomain interaction of GIVA phospholipase A2 as revealed by hydrogen/deuterium exchange mass spectrometry.

Yuan-Hao Hsu, John E Burke, Daren L Stephens, Raymond A Deems, Sheng Li, Kyle M Asmus, Virgil L Woods, Edward A Dennis

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
–field-weighted citation impact
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

30 citing papers in PubMed.

  1. Article
  2. Article
  3. The mechanism of allosteric regulation of calcium-independent phospholipase AProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  4. Review
  5. Article
  6. Dynamic structural biology at the protein membrane interface.The Journal of biological chemistry · 2019
    Review
  7. Article
  8. Synopsis of arachidonic acid metabolism: A review.Journal of advanced research · 2018
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
  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.

Yuan-Hao HsuDepartment of Chemistry and Biochemistry, University of California-San Diego, La Jolla, CA 92093-0601, USA.
John E Burke
Daren L Stephens
Raymond A Deems
Sheng Li
Kyle M Asmus
Virgil L Woods
Edward A Dennis

Funding

ACTION OF LIPOLYTIC ENZYMESR01GM020501 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DENNIS, EDWARD A · 1985 to 2020
$7.3M
Structure and Assembly of Type IV Pili &Related SystemsR01AI022160 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI TAINER, JOHN A. · 1985 to 2009
$3.2M
STRUCTURAL ANALYSIS OF CHROMATICALLY ACTIVE PROTEINSR01GM037684 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI GETZOFF, ELIZABETH D · 1987 to 2009
$3.1M
Enhanced Crystallography of Cancer-Implicated ProteinsR33CA099835 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WOODS, VIRGIL L · 2004 to 2006
$1.8M
DXMS-Facilitated Membrane Protein Construct Design/CancerR21CA118595 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WOODS, VIRGIL L · 2006 to 2007
$420k
Enhanced Crystallography of Cancer-Implicated ProteinsR21CA099835 · NCI · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI WOODS, VIRGIL L · 2003 to 2003
$142k
NCI NIH HHS CA 099835NCI NIH HHS CA 118595NIAID NIH HHS AI 0220221NIAID NIH HHS AI 022160NIGMS NIH HHS GM 037684NIGMS NIH HHS GM 20501NIGMS NIH HHS R01 GM020501
6 · The paper itself

Abstract

The GIVA phospholipase A(2) (PLA(2)) contains two domains: a calcium-binding domain (C2) and a catalytic domain. These domains are linked via a flexible tether. GIVA PLA(2) activity is Ca(2+)-dependent in that calcium binding promotes protein docking to the phospholipid membrane. In addition, the catalytic domain has a lid that covers the active site, presumably regulating GIVA PLA(2) activity. We now present studies that explore the dynamics and conformational changes of this enzyme in solution utilizing peptide amide hydrogen/deuterium (H/D) exchange coupled with liquid chromatography-mass spectrometry (DXMS) to probe the solvent accessibility and backbone flexibility of the C2 domain, the catalytic domain, and the intact GIVA PLA(2). We also analyzed the changes in H/D exchange of the intact GIVA PLA(2) upon Ca(2+) binding. The DXMS results showed a fast H/D-exchanging lid and a slow exchanging central core. The C2 domain showed two distinct regions: a fast exchanging region facing away from the catalytic domain and a slow exchanging region present in the "cleft" region between the C2 and catalytic domains. The slow exchanging region of the C2 domain is in tight proximity to the catalytic domain. The effects of Ca(2+) binding on GIVA PLA(2) are localized in the C2 domain and suggest that binding of two distinct Ca(2+) ions causes tightening up of the regions that surround the anion hole at the tip of the C2 domain. This conformational change may be the initial step in GIVA PLA(2) activation.

Indexed as

AnimalsBinding SitesCalciumCell MembraneChromatography, LiquidDeuteriumEnzyme ActivationHumansHydrogenMass SpectrometryPhospholipases A2Protein BindingProtein Structure, TertiaryCalciumDeuteriumHydrogenPhospholipases A2

Identifiers

PMID18211893
PMCPMC2442293

What OpenQuestion holds

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Registered trials

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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.