1ED5

BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH NNA(H4B FREE)

Summary for 1ED5

• Entry DOI: 10.2210/pdb1ed5/pdb
• Related: 1ED4 1ED6 8NSE
• Descriptor: NITRIC OXIDE SYNTHASE, ACETATE ION, PROTOPORPHYRIN IX CONTAINING FE, ... (8 entities in total)
• Functional Keywords: nitric oxide synthase, heme protein, alpha-beta fold, oxidoreductase
• Biological source: Bos taurus (cattle)
• Cellular location: Cell membrane: P29473
• Total number of polymer chains: 2
• Total formula weight: 101919.45

Authors

Raman, C.S.,Li, H.,Martasek, P.,Southan, G.J.,Masters, B.S.S.,Poulos, T.L. (deposition date: 2000-01-26, release date: 2001-01-31, Last modification date: 2023-11-15)

Primary citation

Raman, C.S.,Li, H.,Martasek, P.,Southan, G.,Masters, B.S.,Poulos, T.L.
Crystal structure of nitric oxide synthase bound to nitro indazole reveals a novel inactivation mechanism.
Biochemistry, 40:13448-13455, 2001

PubMed 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.

PubMed: 11695891
DOI: 10.1021/bi010957u

Experimental method

X-RAY DIFFRACTION (1.8 Å)