ArticleThe EMBO journal2003
Structural basis for endothelial nitric oxide synthase binding to calmodulin.
Article in The EMBO journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 72 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Neurotoxic Effects of Neonicotinoids on Mammals: What Is There beyond the Activation of Nicotinic Acetylcholine Receptors?-A Systematic Review.International journal of molecular sciences · 2021Pooled it
- A sensitive orange fluorescent calcium ion indicator for imaging neural activity.Nature communications · 2026Article
- Nitric Oxide Signaling in Cardiovascular Physiology and Pathology: Mechanisms, Dysregulation, and Therapeutic Frontiers.International journal of molecular sciences · 2026Review
- Article
- The Ever-Expanding Influence of the Endothelial Nitric Oxide Synthase.Basic & clinical pharmacology & toxicology · 2025Review
- Selectively targeting the AdipoR2-CaM-CaMKII-NOS3 axis by SCM-198 as a rapid-acting therapy for advanced acute liver failure.Nature communications · 2024Article
- An integrative approach to protein sequence design through multiobjective optimization.PLoS computational biology · 2024Article
- Lipid Emulsions Inhibit Labetalol-Induced Vasodilation in the Isolated Rat Aorta.International journal of molecular sciences · 2024Article
- Modulating Nitric Oxide: Implications for Cytotoxicity and Cytoprotection.Antioxidants (Basel, Switzerland) · 2024Review
- Influencing Endothelial Cells' Roles in Inflammation and Wound Healing Through Nucleic Acid Delivery.Tissue engineering. Part A · 2024Review
- Review
- Insights into human eNOS, nNOS and iNOS structures and medicinal indications from statistical analyses of their interactions with bound compounds.Biophysics reports · 2023Article
- Structures of calmodulin-melittin complexes show multiple binding modes lacking classical anchoring interactions.The Journal of biological chemistry · 2023Article
- Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets.Cellular & molecular biology letters · 2023Article
- Beyond its Psychiatric Use: The Benefits of Low-dose Lithium Supplementation.Current neuropharmacology · 2023Review
- Therapeutics effect of mesenchymal stromal cells in reactive oxygen species-induced damages.Human cell · 2022Review
- Neuropsychiatric Symptoms of COVID-19 Explained by SARS-CoV-2 Proteins' Mimicry of Human Protein Interactions.Frontiers in human neuroscience · 2021Article
- Navigating Calcium and Reactive Oxygen Species by Natural Flavones for the Treatment of Heart Failure.Frontiers in pharmacology · 2021Review
- P2Y Purinergic Receptors, Endothelial Dysfunction, and Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Positional Distributions of the Tethered Modules in Nitric Oxide Synthase: Monte Carlo Calculations and Pulsed EPR Measurements.The journal of physical chemistry. A · 2019Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
4 authors.
Funding
Abstract
The enzyme nitric oxide synthase (NOS) is exquisitely regulated in vivo by the Ca(2+) sensor protein calmodulin (CaM) to control production of NO, a key signaling molecule and cytotoxin. The differential activation of NOS isozymes by CaM has remained enigmatic, despite extensive research. Here, the crystallographic structure of Ca(2+)-loaded CaM bound to a 20 residue peptide comprising the endothelial NOS (eNOS) CaM-binding region establishes their individual conformations and intermolecular interactions, and suggests the basis for isozyme-specific differences. The alpha-helical eNOS peptide binds in an antiparallel orientation to CaM through extensive hydrophobic interactions. Unique NOS interactions occur with: (i). the CaM flexible central linker, explaining its importance in NOS activation; and (ii). the CaM C-terminus, explaining the NOS-specific requirement for a bulky, hydrophobic residue at position 144. This binding mode expands mechanisms for CaM-mediated activation, explains eNOS deactivation by Thr495 phosphorylation, and implicates specific hydrophobic residues in the Ca(2+) independence of inducible NOS.
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Registered trials
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.