HUMAN ENDOTHELIAL NITRIC OXIDE SYNTHASE WITH ARGININE SUBSTRATE

File:3nos.jpg


3nos, resolution 2.400Å

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OverviewOverview

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.

DiseaseDisease

Known diseases associated with this structure: Alzheimer disease, late-onset, susceptibility to OMIM:[163729], Coronary spasms, susceptibility to OMIM:[163729], Hypertension, pregnancy-induced OMIM:[163729], Hypertension, susceptibility to OMIM:[163729], Ischemic stroke, susceptibility to OMIM:[163729], Placental abruption OMIM:[163729]

About this StructureAbout this Structure

3NOS is a Single protein structure of sequence from Homo sapiens with , , and as ligands. Active as Nitric-oxide synthase, with EC number 1.14.13.39 Full crystallographic information is available from OCA.

ReferenceReference

Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation., Fischmann TO, Hruza A, Niu XD, Fossetta JD, Lunn CA, Dolphin E, Prongay AJ, Reichert P, Lundell DJ, Narula SK, Weber PC, Nat Struct Biol. 1999 Mar;6(3):233-42. PMID:10074942

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