1D0C

BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 3-BROMO-7-NITROINDAZOLE (H4B FREE)

Summary for 1D0C

• Entry DOI: 10.2210/pdb1d0c/pdb
• Related: 1D0C 1D0O 1D1V 1D1W 1D1X 1D1Y 1NSE
• Descriptor: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN, ACETATE ION, ZINC ION, ... (8 entities in total)
• Functional Keywords: alpha-beta fold, oxidoreductase
• Biological source: Bos taurus (cattle)
• Cellular location: Cell membrane: P29473
• Total number of polymer chains: 2
• Total formula weight: 102383.07

Authors

Raman, C.S.,Li, H.,Martasek, P.,Southan, G.J.,Masters, B.S.S.,Poulos, T.L. (deposition date: 1999-09-09, release date: 2001-11-21, 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 (1.65 Å)