Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedNitric 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences | ||||||||||||||||||||||
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