3nos

From Proteopedia

Jump to: navigation, search

HUMAN ENDOTHELIAL NITRIC OXIDE SYNTHASE WITH ARGININE SUBSTRATE

Structural highlights

3nos is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.4Å
Ligands:H4B, HAR, HEM, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NOS3_HUMAN Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.[1] Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..
Citations
50 reviews cite this structure
Nitric oxide synthases: structure, function and inhibition.
Alderton et al. (2001)
49 more
142 other articles
No citations found

See Also

References

  1. ↑ Lorenz M, Hewing B, Hui J, Zepp A, Baumann G, Bindereif A, Stangl V, Stangl K. Alternative splicing in intron 13 of the human eNOS gene: a potential mechanism for regulating eNOS activity. FASEB J. 2007 May;21(7):1556-64. Epub 2007 Jan 30. PMID:17264164 doi:http://dx.doi.org/10.1096/fj.06-7434com
  2. ↑ Lorenz M, Hewing B, Hui J, Zepp A, Baumann G, Bindereif A, Stangl V, Stangl K. Alternative splicing in intron 13 of the human eNOS gene: a potential mechanism for regulating eNOS activity. FASEB J. 2007 May;21(7):1556-64. Epub 2007 Jan 30. PMID:17264164 doi:http://dx.doi.org/10.1096/fj.06-7434com
  3. ↑ Fischmann TO, Hruza A, Niu XD, Fossetta JD, Lunn CA, Dolphin E, Prongay AJ, Reichert P, Lundell DJ, Narula SK, Weber PC. Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation. Nat Struct Biol. 1999 Mar;6(3):233-42. PMID:10074942 doi:http://dx.doi.org/10.1038/6675

Contents


PDB ID 3nos

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/3nos"
Personal tools