1FOJ

BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 7-NITROINDAZOLE-2-CARBOXAMIDINE (H4B PRESENT)

Summary for 1FOJ

• Entry DOI: 10.2210/pdb1foj/pdb
• Descriptor: NITRIC-OXIDE SYNTHASE, CACODYLATE ION, ACETATE ION, ... (8 entities in total)
• Functional Keywords: alpha-beta fold, nitric oxide synthase, oxidoreductase
• Biological source: Bos taurus (cattle)
• Cellular location: Cell membrane: P29473
• Total number of polymer chains: 2
• Total formula weight: 101965.36

Authors

Raman, C.S.,Li, H.,Martasek, P.,Masters, B.S.,Poulos, T.L. (deposition date: 2000-08-28, release date: 2001-11-16, Last modification date: 2024-02-07)

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 (2.1 Å)