Evidence map›Paper›PMID 25286850›Full record

ArticleActa crystallographica. Section D, Biological crystallography2014

Structures of human constitutive nitric oxide synthases.

Huiying Li, Joumana Jamal, Carla Plaza, Stephanie Hai Pineda, Georges Chreifi, Qing Jing, Maris A Cinelli, Richard B Silverman, Thomas L Poulos

Open access · bronzeAbstract read
In one paragraph

Article in Acta crystallographica. Section D, Biological crystallography, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.4field-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

26 citing papers in PubMed, 41 citations in OpenAlex.

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  4. Molecules (Basel, Switzerland) · 2023
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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

9 authors at 2 institutions in 1 country.

Huiying LiDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences and Chemistry, University of California, Irvine, 517 Bison Avenue, Irvine, CA 92697-3900, USA.
Joumana JamalDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences and Chemistry, University of California, Irvine, 517 Bison Avenue, Irvine, CA 92697-3900, USA.
Carla PlazaDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences and Chemistry, University of California, Irvine, 517 Bison Avenue, Irvine, CA 92697-3900, USA.
Stephanie Hai PinedaDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences and Chemistry, University of California, Irvine, 517 Bison Avenue, Irvine, CA 92697-3900, USA.
Georges ChreifiDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences and Chemistry, University of California, Irvine, 517 Bison Avenue, Irvine, CA 92697-3900, USA.
Qing JingDepartment of Chemistry and Department of Molecular Biosciences, Chemistry of Life Processes Institute, Center for Molecular Innovation and Drug Discovery, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208-3113, USA.
Maris A CinelliDepartment of Chemistry and Department of Molecular Biosciences, Chemistry of Life Processes Institute, Center for Molecular Innovation and Drug Discovery, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208-3113, USA.
Richard B SilvermanDepartment of Chemistry and Department of Molecular Biosciences, Chemistry of Life Processes Institute, Center for Molecular Innovation and Drug Discovery, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208-3113, USA.
Thomas L PoulosDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences and Chemistry, University of California, Irvine, 517 Bison Avenue, Irvine, CA 92697-3900, USA.
University of California, Irvine · USNorthwestern University · US

Funding

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
Design, Synthesis, and Biology of Inhibitors of Neuronal Nitric Oxide SynthaseF32GM109667 · NIGMS · NORTHWESTERN UNIVERSITY · PI CINELLI, MARIS A · 2014 to 2015
$109k
NIGMS NIH HHS F32 GM109667NIGMS NIH HHS GM049725NIGMS NIH HHS GM57353NIGMS NIH HHS R01 GM049725NIGMS NIH HHS R01 GM057353
6 · The paper itself

Abstract

Mammals produce three isoforms of nitric oxide synthase (NOS): neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The overproduction of NO by nNOS is associated with a number of neurodegenerative disorders; therefore, a desirable therapeutic goal is the design of drugs that target nNOS but not the other isoforms. Crystallography, coupled with computational approaches and medicinal chemistry, has played a critical role in developing highly selective nNOS inhibitors that exhibit exceptional neuroprotective properties. For historic reasons, crystallography has focused on rat nNOS and bovine eNOS because these were available in high quality; thus, their structures have been used in structure-activity-relationship studies. Although these constitutive NOSs share more than 90% sequence identity across mammalian species for each NOS isoform, inhibitor-binding studies revealed that subtle differences near the heme active site in the same NOS isoform across species still impact enzyme-inhibitor interactions. Therefore, structures of the human constitutive NOSs are indispensible. Here, the first structure of human neuronal NOS at 2.03 Å resolution is reported and a different crystal form of human endothelial NOS is reported at 1.73 Å resolution.

Indexed as

AminopyridinesAnimalsCatalytic DomainCattleCloning, MolecularCrystallography, X-RayEnzyme InhibitorsHemeHumansModels, MolecularNitric Oxide Synthase Type INitric Oxide Synthase Type IIIProtein Structure, TertiaryPyrrolidinesRatsAminopyridinesEnzyme InhibitorsHemeNitric Oxide Synthase Type INitric Oxide Synthase Type IIINOS1 protein, humanNOS3 protein, humanPyrrolidinesnitric oxide synthase

Identifiers

PMID25286850
PMCPMC4188008
OpenAlexW1969385243

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.