1ED5: Bovine Endothelial Nitric Oxide Synthase Heme Domain Complexed With Nna(H4b Free)

Citation:
Abstract
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.
PDB ID: 1ED5Download
MMDB ID: 15277
PDB Deposition Date: 2000/1/26
Updated in MMDB: 2001/12
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 1ED5: dimeric; determined by author and by software (PISA)
Molecular Components in 1ED5
Label Count Molecule
Proteins (2 molecules)
2
Nitric Oxide Synthase(Gene symbol: NOS3)
Molecule annotation
Chemicals (13 molecules)
1
2
2
2
3
2
4
2
5
4
6
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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