| Literature DB >> 10074942 |
T O Fischmann1, A Hruza, X D Niu, J D Fossetta, C A Lunn, E Dolphin, A J Prongay, P Reichert, D J Lundell, S K Narula, P C Weber.
Abstract
Crystal structures of human endothelial nitric oxide synthase (eNOS) and human inducible NOS (iNOS) catalytic domains were solved in complex with the arginine substrate and an inhibitor S-ethylisothiourea (SEITU), respectively. The small molecules bind in a narrow cleft within the larger active-site cavity containing heme and tetrahydrobiopterin. Both are hydrogen-bonded to a conserved glutamate (eNOS E361, iNOS E377). The active-site residues of iNOS and eNOS are nearly identical. Nevertheless, structural comparisons provide a basis for design of isozyme-selective inhibitors. The high-resolution, refined structures of eNOS (2.4 A resolution) and iNOS (2.25 A resolution) reveal an unexpected structural zinc situated at the intermolecular interface and coordinated by four cysteines, two from each monomer.Entities:
Mesh：
Substances：
Year: 1999 PMID： 10074942 DOI： 10.1038/6675
Source DB: PubMed Journal: Nat Struct Biol ISSN： 1072-8368