Evidence map›Paper›PMID 26091171›Full record

ArticleChemistry & biology2015

Nitric Oxide Synthase as a Target for Methicillin-Resistant Staphylococcus aureus.

Jeffrey K Holden, Soosung Kang, Federico C Beasley, Maris A Cinelli, Huiying Li, Saurabh G Roy, Dillon Dejam, Aimee L Edinger, Victor Nizet, Richard B Silverman and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chemistry & biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

16 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Article
  3. Nicorandil reduces the antimicrobial effectiveness of polymyxin E againstFrontiers in cellular and infection microbiology · 2025
    Article
  4. Article
  5. Review
  6. The nitric oxide synthase gene negatively regulates biofilm formation inFrontiers in cellular and infection microbiology · 2022
    Article
  7. Article
  8. The Response ofJournal of bacteriology · 2019
    Article
  9. Article
  10. Article
  11. Nitric oxide synthase and structure-based inhibitor design.Nitric oxide : biology and chemistry · 2017
    Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. 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

11 authors at 3 institutions in 1 country.

Jeffrey K HoldenDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences, and Chemistry, University of California, Irvine, CA 92697-3900, USA.
Soosung KangDepartments of Chemistry and Molecular Biosciences, Chemistry of Life Processes Institute, Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, IL 60208-3113, USA.
Federico C BeasleyDepartments of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA 92093, USA.
Maris A CinelliDepartments of Chemistry and Molecular Biosciences, Chemistry of Life Processes Institute, Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, IL 60208-3113, USA.
Huiying LiDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences, and Chemistry, University of California, Irvine, CA 92697-3900, USA.
Saurabh G RoyDepartment of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA.
Dillon DejamDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences, and Chemistry, University of California, Irvine, CA 92697-3900, USA.
Aimee L EdingerDepartment of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA.
Victor NizetDepartments of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA 92093, USA.
Richard B SilvermanDepartments of Chemistry and Molecular Biosciences, Chemistry of Life Processes Institute, Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, IL 60208-3113, USA. Electronic address: agman@chem.northwestern.edu.
Thomas L PoulosDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences, and Chemistry, University of California, Irvine, CA 92697-3900, USA. Electronic address: poulos@uci.edu.
University of California, Irvine · USNorthwestern University · USUniversity of California San Diego · US

Funding

Vaccines and Therapies Against BotulismU54AI057153 · NIAID · UNIVERSITY OF CHICAGO · PI SHUMAN, HOWARD A · 2003 to 2013
$87.6M
STRUCTURAL STUDIES ON NITRIC OXIDE SYNTHASER01GM057353 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI POULOS, THOMAS L · 1998 to 2018
$6.8M
Selective inhibition of nitric oxide synthase for multiple indicationsR01GM049725 · NIGMS · NORTHWESTERN UNIVERSITY · PI SILVERMAN, RICHARD B · 1994 to 2018
$6.0M
TRAINING & OUTREACH COREU54HD071600 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BEST, BROOKIE MANNING · 2011 to 2015
$3.6M
NIAID NIH HHS AI057153NIAID NIH HHS U54 AI057153NICHD NIH HHS HD071600NICHD NIH HHS U54 HD071600NIGMS NIH HHS GM49725NIGMS NIH HHS GM57353NIGMS NIH HHS R01 GM049725NIGMS NIH HHS R01 GM057353
6 · The paper itself

Abstract

Bacterial infections associated with methicillin-resistant Staphylococcus aureus (MRSA) are a major economic burden to hospitals, and confer high rates of morbidity and mortality among those infected. Exploitation of novel therapeutic targets is thus necessary to combat this dangerous pathogen. Here, we report on the identification and characterization, including crystal structures, of two nitric oxide synthase (NOS) inhibitors that function as antimicrobials against MRSA. These data provide the first evidence that bacterial NOS (bNOS) inhibitors can work synergistically with oxidative stress to enhance MRSA killing. Crystal structures show that each inhibitor contacts an active site Ile residue in bNOS that is Val in the mammalian NOS isoforms. Mutagenesis studies show that the additional nonpolar contacts provided by the Ile in bNOS contribute to tighter binding toward the bacterial enzyme.

Indexed as

AnimalsBacterial ProteinsBinding SitesCell LineCell SurvivalDatabases, ProteinEnzyme InhibitorsKineticsMethicillin-Resistant Staphylococcus aureusMiceMolecular Docking SimulationMutagenesisNitric Oxide SynthaseProtein BindingProtein IsoformsBacterial ProteinsEnzyme InhibitorsNitric Oxide SynthaseProtein Isoforms

Identifiers

PMID26091171
PMCPMC4475277
OpenAlexW2137584539

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.