Nitric oxide synthases: structure, function and inhibition
Open accessAbstract
This review concentrates on advances in nitric oxide synthase (NOS) structure, function and inhibition made in the last seven years, during which time substantial advances have been made in our understanding of this enzyme family. There is now information on the enzyme structure at all levels from primary (amino acid sequence) to quaternary (dimerization, association with other proteins) structure. The crystal structures of the oxygenase domains of inducible NOS (iNOS) and vascular endothelial NOS (eNOS) allow us to interpret other information in the context of this important part of the enzyme, with its binding sites for iron protoporphyrin IX (haem), biopterin, l-arginine, and the many inhibitors which interact with them. The exact nature of the NOS reaction, its mechanism and its products continue to be sources of controversy. The role of the biopterin cofactor is now becoming clearer, with emerging data implicating one-electron redox cycling as well as the multiple allosteric effects on enzyme activity. Regulation of the NOSs has been described at all levels from gene transcription to covalent modification and allosteric regulation of the enzyme itself. A wide range of NOS inhibitors have been discussed, interacting with the enzyme in diverse ways in terms of site and mechanism of inhibition, time-dependence and selectivity for individual isoforms, although there are many pitfalls and misunderstandings of these aspects. Highly selective inhibitors of iNOS versus eNOS and neuronal NOS have been identified and some of these have potential in the treatment of a range of inflammatory and other conditions in which iNOS has been implicated.
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NO is synthesized intracellularly through the action of a family of NOS enzymes.
“NO is synthesized intracellularly through the action of a family of NOS enzymes (25).”
From What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology (2010) · cites this paper as [25]
The most common route of NO production is through the action of the nitric oxide synthase family of enzymes.
“The most common route of NO production is through the action of the nitric oxide synthase (NOS) family of enzymes [62, 64].”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [64]
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- Authors
- ALDERTON, W. K., COOPER, C. E., & KNOWLES, R. G.
- Affiliations
- GlaxoSmithKline (United Kingdom) (GB)
- University of Essex (GB)
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2001-07-25
- Volume
- 357
- Issue
- 3
- Pages
- 593-615
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1221991
- OpenAlex
- W2115153703
- Cited by
- 4,110
- References
- 0
- Citations by year
- 2026: 57 · 2025: 89 · 2024: 100 · 2023: 121 · 2022: 137 · 2021: 128 · 2020: 149 · 2019: 142 · 2018: 145 · 2017: 172 · 2016: 176 · 2015: 174 · 2014: 187 · 2013: 203 · 2012: 227
- FWCI
- 16.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Keywords
- nitric oxide synthase, inducible nitric oxide synthase, endothelial nitric oxide synthase, neuronal nitric oxide synthase, enzyme structure, oxygenase domain, heme binding, enzyme mechanism, allosteric regulation, enzyme inhibition, isoform-selective inhibitors
- MeSH terms
- Animals, Catalysis, Humans, Isoenzymes, Models, Molecular, Nitric Oxide, Gene Expression Regulation, Enzymologic, Alternative Splicing, Protein Structure, Tertiary, Nitric Oxide Synthase, Dimerization
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