1ed5
BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH NNA(H4B FREE)
| |||||||
| , resolution 1.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , , | ||||||
| Activity: | Nitric-oxide synthase, with EC number 1.14.13.39 | ||||||
| Related: | 8NSE, 1ED4, 1ED6
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
1ED5 is a Single protein structure of sequence from Bos taurus. 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
Page seeded by OCA on Sun Mar 30 20:00:10 2008