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OverviewIn order to make further progress in elucidating the mechanism of NOS catalysis it will be essential to throw light on the interaction between the enzyme and its substrate. An understanding of the catalytic site will also assist the development of therapeutically important NOS inhibitors. In particular. it will be useful to uncover any differences that exist between the substrate binding sites of the three NOS isozymes which might be exploited for the development of isoform selective NOS inhibitors. A comparison of NOS to other Arg-binding proteins has shown no significant sequence homology (159). Moreover, the lack of a 3D structure and absence of significant sequence homology between the NOS oxygenase domain and known cytochromes P450 has made it difficult to identify residues and construct a model of the distal heme pocket responsible for substrate binding. However, a number of groups are currently working towards crystallisation of the separate NOS reductase and oxygenase domains of the three isoforms for X-ray diffraction studies; the first X-ray structure is likely to be forthcoming within a matter of months. * The results of these studies are expected to resolve many of the uncertainties surrounding the structure of the NOS catalytic site. Preliminary X-ray diffraction analysis of CPR from rat liver has already been reported by MASTERS et al. (524) and the future emergence of a detailed structure for this protein should throw light on the structure and function of the NOS reductase domain. Full Product DetailsAuthor: D.R. Adams , M. Brochwicz-Lewinski , A.R. ButlerPublisher: Springer Verlag GmbH Imprint: Springer Verlag GmbH Edition: Softcover reprint of the original 1st ed. 1999 Volume: 76 Dimensions: Width: 15.50cm , Height: 1.20cm , Length: 23.50cm Weight: 0.355kg ISBN: 9783709173053ISBN 10: 3709173051 Pages: 211 Publication Date: 08 October 2012 Audience: Professional and scholarly , Professional & Vocational Format: Paperback Publisher's Status: Active Availability: In Print This item will be ordered in for you from one of our suppliers. Upon receipt, we will promptly dispatch it out to you. For in store availability, please contact us. Table of ContentsNitric Oxide: Physiological Roles, Biosynthesis and Medical Uses.- List of Abbreviations and Acronyms.- 1. Introduction.- 2. Discovery in the Vasculature.- 3. Platelet Aggregation.- 4. NO and the Immune System.- 5. NO and the Nervous System.- 6. S-Nitrosothiols.- 7. NO Activity in the Mammalian Eye.- 8. The NO Biosynthetic Pathway.- 9. Mechanism of the Nitric Oxide Synthase-Catalysed Reaction.- 10. Nitric Oxide Synthase Structure.- 11. Clinical Uses of NO and Its Inhibitors.- 12. Addendum.- Acknowledgements.- References.- Author Index.ReviewsAuthor InformationTab Content 6Author Website:Countries AvailableAll regions |