1foj
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BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 7-NITROINDAZOLE-2-CARBOXAMIDINE (H4B PRESENT)
OverviewOverview
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 StructureAbout this Structure
1FOJ is a Single protein structure of sequence from Bos taurus with CAC, ACT, ZN, HEM, 7NI and 7I2 as ligands. Active as Nitric-oxide synthase, with EC number 1.14.13.39 Full crystallographic information is available from OCA.
ReferenceReference
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
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