Evidence map›Paper›PMID 24003111›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Nitric oxide synthase domain interfaces regulate electron transfer and calmodulin activation.

Brian C Smith, Eric S Underbakke, Daniel W Kulp, William R Schief, Michael A Marletta

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
5.5field-weighted citation impact, top 4% 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

53 citing papers in PubMed, 98 citations in OpenAlex.

  1. Review
  2. Article
  3. iNOS in Macrophage Polarization: Pharmacological and Regulatory Insights.International journal of molecular sciences · 2025
    Review
  4. Detection of a clamp-shaped conformation of a neuronal nitric oxide synthase construct by pulsed EPR.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2025
    Article
  5. Article
  6. Analyzing the FMN-heme interdomain docking interactions in neuronal and inducible NOS isoforms by pulsed EPR experiments and conformational distribution modeling.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2024
    Article
  7. Article
  8. Probing calmodulin-NO synthase interactions via site-specific infrared spectroscopy: an introductory investigation.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2024
    Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Astrocyte Intracellular CaNeurotoxicity research · 2021
    Article
  15. Review
  16. Article
  17. Review
  18. An isoform-specific pivot modulates the electron transfer between the flavin mononucleotide and heme centers in inducible nitric oxide synthase.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020
    Article
  19. NADSignal transduction and targeted therapy · 2020
    Review
  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

5 authors at 1 institution in 1 country.

Brian C SmithDepartments of Chemistry and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
Eric S Underbakke
Daniel W Kulp
William R Schief
Michael A Marletta
Scripps Research Institute · US

Funding

QTOF MASS SPECTROMETER: CELL MOLECULAR BIOLOGY, PROTEIN STRUCTURES10RR022393 · NCRR · UNIVERSITY OF CALIFORNIA BERKELEY · PI WILLIAMS, EVAN R · 2006 to 2006
$499k
Mapping The Domain Architecture And Conformations of Soluble Guanylate CyclaseF32GM093564 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI UNDERBAKKE, ERIC STEVEN · 2010 to 2012
$126k
Shining Light on the Mechanism and Regulation of Nitric Oxide SynthasesF32GM095023 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI SMITH, BRIAN CHRISTOPHER · 2010 to 2012
$115k
NCRR NIH HHS 1S10RR022393-01NCRR NIH HHS S10 RR022393NIGMS NIH HHS 5F32GM093564NIGMS NIH HHS 5F32GM095023NIGMS NIH HHS F32 GM093564NIGMS NIH HHS F32 GM095023
6 · The paper itself

Abstract

Nitric oxide (NO) produced by NO synthase (NOS) participates in diverse physiological processes such as vasodilation, neurotransmission, and the innate immune response. Mammalian NOS isoforms are homodimers composed of two domains connected by an intervening calmodulin-binding region. The N-terminal oxidase domain binds heme and tetrahydrobiopterin and the arginine substrate. The C-terminal reductase domain binds FAD and FMN and the cosubstrate NADPH. Although several high-resolution structures of individual NOS domains have been reported, a structure of a NOS holoenzyme has remained elusive. Determination of the higher-order domain architecture of NOS is essential to elucidate the molecular underpinnings of NO formation. In particular, the pathway of electron transfer from FMN to heme, and the mechanism through which calmodulin activates this electron transfer, are largely unknown. In this report, hydrogen-deuterium exchange mass spectrometry was used to map critical NOS interaction surfaces. Direct interactions between the heme domain, the FMN subdomain, and calmodulin were observed. These interaction surfaces were confirmed by kinetic studies of site-specific interface mutants. Integration of the hydrogen-deuterium exchange mass spectrometry results with computational docking resulted in models of the NOS heme and FMN subdomain bound to calmodulin. These models suggest a pathway for electron transfer from FMN to heme and a mechanism for calmodulin activation of this critical step.

Indexed as

Models, MolecularProtein ConformationAnimalsCalmodulinDeuterium Exchange MeasurementDimerizationElectron TransportElectrophoresis, Polyacrylamide GelFlavin-Adenine DinucleotideFlavin MononucleotideFluorescenceHemeMass SpectrometryNitric Oxide Synthase Type IISpecies SpecificityCalmodulinFlavin-Adenine DinucleotideFlavin MononucleotideHemeNitric Oxide Synthase Type IIflavinhemoproteiniNOSNO signaling

Identifiers

PMID24003111
PMCPMC3780838
OpenAlexW1997386174

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.