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Related Experiment Videos

Nitric oxide synthases: structure, function and inhibition.

W K Alderton1, C E Cooper, R G Knowles

  • 1In Vitro Pharmacology Department, GlaxoSmithKline Research and Development, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK.

The Biochemical Journal
|July 21, 2001
PubMed
Summary
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Recent advances in nitric oxide synthase (NOS) research reveal new insights into enzyme structure, function, and inhibition. Highly selective inhibitors targeting inducible NOS (iNOS) show therapeutic potential for inflammatory conditions.

Area of Science:

  • Biochemistry and Molecular Biology
  • Enzymology
  • Pharmacology

Background:

  • Nitric oxide synthases (NOS) are crucial enzymes involved in various physiological and pathological processes.
  • Understanding NOS structure, function, and regulation is key to developing targeted therapies.
  • Recent years have seen significant progress in elucidating the complexities of the NOS enzyme family.

Purpose of the Study:

  • To review recent advances in the structure, function, and inhibition of nitric oxide synthase (NOS) enzymes.
  • To highlight new understandings of enzyme mechanisms, cofactor roles, and regulatory pathways.
  • To discuss the development and potential therapeutic applications of novel NOS inhibitors.

Main Methods:

  • Comprehensive review of literature published in the last seven years.

Related Experiment Videos

  • Analysis of structural data, including crystal structures of inducible NOS (iNOS) and endothelial NOS (eNOS) oxygenase domains.
  • Examination of studies on enzyme kinetics, reaction mechanisms, cofactor roles, and regulatory mechanisms.

    • Main Results:

    • Detailed structural information is available from primary to quaternary levels for NOS enzymes.
    • Crystal structures of iNOS and eNOS oxygenase domains provide insights into binding sites for substrates, cofactors, and inhibitors.
    • Emerging data clarifies the role of the biopterin cofactor and implicates one-electron redox cycling in NOS activity.
    • Regulation of NOS occurs at multiple levels, including gene transcription, covalent modification, and allosteric effects.
    • A diverse array of NOS inhibitors has been developed, with varying mechanisms, selectivity, and time-dependence.
    • Highly selective inhibitors for iNOS, eNOS, and neuronal NOS (nNOS) have been identified.

    Conclusions:

    • Significant progress has been made in understanding NOS structure, function, and regulation.
    • Despite advances, controversies regarding the NOS reaction mechanism and products persist.
    • Selective NOS inhibitors, particularly those targeting iNOS, hold promise for treating inflammatory and other conditions.