8nse: Difference between revisions
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'''BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE, NNA COMPLEX''' | '''BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE, NNA COMPLEX''' | ||
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[[Category: Poulos, T L.]] | [[Category: Poulos, T L.]] | ||
[[Category: Raman, C S.]] | [[Category: Raman, C S.]] | ||
[[Category: | [[Category: Heme protein]] | ||
[[Category: | [[Category: Nitric oxide synthase]] | ||
[[Category: | [[Category: Tetrahydrobiopterin]] | ||
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Revision as of 19:51, 4 May 2008
BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE, NNA COMPLEX
Overview
Nitric oxide is generated under normal and pathophysiological conditions by three distinct isoforms of nitric oxide synthase (NOS). A small-molecule inhibitor of NOS (3-Br-7-nitroindazole, 7-NIBr) is profoundly neuroprotective in mouse models of stroke and Parkinson's disease. We report the crystal structure of the catalytic heme domain of endothelial NOS complexed with 7-NIBr at 1.65 A resolution. Critical to the binding of 7-NIBr at the substrate site is the adoption by eNOS of an altered conformation, in which a key glutamate residue swings out toward one of the heme propionate groups. Perturbation of the heme propionate ensues and eliminates the cofactor tetrahydrobiopterin-heme interaction. We also present three crystal structures that reveal how alterations at the substrate site facilitate 7-NIBr and structurally dissimilar ligands to occupy the cofactor site.
About this Structure
8NSE is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
Reference
Crystal structure of nitric oxide synthase bound to nitro indazole reveals a novel inactivation mechanism., Raman CS, Li H, Martasek P, Southan G, Masters BS, Poulos TL, Biochemistry. 2001 Nov 13;40(45):13448-55. PMID:11695891 Page seeded by OCA on Sun May 4 22:51:14 2008
