NOSs (nitric oxide synthases) are flavohaem enzymes that function broadly in human health and disease. We are combining mutagenesis, crystallographic and rapid kinetic methods to understand their mechanism and regulation. The NOSs create a transient tetrahydrobiopterin radical within the enzyme to generate their free radical product (NO). Recent work is revealing how critically important this process is at all levels of catalysis. This article will synthesize four seemingly disparate but related aspects of NOS tetrahydrobiopterin radical formation: (i) how it enables productive O2 activation by providing an electron to the enzyme haem, (ii) what structural features help to regulate this electron transfer, (iii) how it enables NOS to synthesize NO from its diamagnetic substrate and (iv) how it allows NOS to release NO after each catalytic cycle instead of other nitorgen oxide-containing products.
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March 2004
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Conference Article|
March 01 2004
Radical reactions of nitric oxide synthases
Dennis J. Stuehr;
Dennis J. Stuehr
1
*Department of Immunology, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, U.S.A.
1To whom correspondence should be addressed (e-mail [email protected]).
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Chin-Chuan Wei;
Chin-Chuan Wei
*Department of Immunology, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, U.S.A.
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Jerome Santolini;
Jerome Santolini
*Department of Immunology, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, U.S.A.
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Zhi- Qiang Wang;
Zhi- Qiang Wang
*Department of Immunology, Lerner Research Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, U.S.A.
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Mika Aoyagi;
Mika Aoyagi
†Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, U.S.A.
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Elizabeth D. Getzoff
Elizabeth D. Getzoff
†Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, U.S.A.
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Publisher: Portland Press Ltd
Online ISSN: 1744-1439
Print ISSN: 0067-8694
© 2004 The Biochemical Society
2004
Biochem Soc Symp (2004) 71: 39–49.
Citation
Chris Cooper, Mike Wilson, Victor Darley-Usmar, Dennis J. Stuehr, Chin-Chuan Wei, Jerome Santolini, Zhi- Qiang Wang, Mika Aoyagi, Elizabeth D. Getzoff; Radical reactions of nitric oxide synthases. Biochem Soc Symp 1 March 2004; 71 39–49. doi: https://doi.org/10.1042/bss0710039
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