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New page: left|200px<br /><applet load="2nse" size="450" color="white" frame="true" align="right" spinBox="true" caption="2nse, resolution 2.34Å" /> '''BOVINE ENDOTHELIAL N...
 
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'''BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE SUBSTRATE COMPLEX'''<br />


==Overview==
==BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE SUBSTRATE COMPLEX==
Nitric oxide, a key signaling molecule, is produced by a family of enzymes, collectively called nitric oxide synthases (NOS). Here, we report the, crystal structure of the heme domain of endothelial NOS in, tetrahydrobiopterin (H4B)-free and -bound forms at 1.95 A and 1.9 A, resolution, respectively. In both structures a zinc ion is tetrahedrally, coordinated to pairs of symmetry-related cysteine residues at the dimer, interface. The phylogenetically conserved Cys-(X)4-Cys motif and its, strategic location establish a structural role for the metal center in, maintaining the integrity of the H4B-binding site. The unexpected, recognition of the substrate, L-arginine, at the H4B site indicates that, this site is poised to stabilize a positively charged pterin ring and, suggests a model involving a cationic pterin radical in the catalytic, cycle.
<StructureSection load='2nse' size='340' side='right'caption='[[2nse]], [[Resolution|resolution]] 2.34&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2nse]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. The January 2011 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Nitric Oxide Synthase''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2011_1 10.2210/rcsb_pdb/mom_2011_1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NSE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NSE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.34&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ARG:ARGININE'>ARG</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2nse FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nse OCA], [https://pdbe.org/2nse PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nse RCSB], [https://www.ebi.ac.uk/pdbsum/2nse PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nse ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NOS3_BOVIN NOS3_BOVIN] 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.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ns/2nse_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2nse ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Nitric oxide, a key signaling molecule, is produced by a family of enzymes collectively called nitric oxide synthases (NOS). Here, we report the crystal structure of the heme domain of endothelial NOS in tetrahydrobiopterin (H4B)-free and -bound forms at 1.95 A and 1.9 A resolution, respectively. In both structures a zinc ion is tetrahedrally coordinated to pairs of symmetry-related cysteine residues at the dimer interface. The phylogenetically conserved Cys-(X)4-Cys motif and its strategic location establish a structural role for the metal center in maintaining the integrity of the H4B-binding site. The unexpected recognition of the substrate, L-arginine, at the H4B site indicates that this site is poised to stabilize a positively charged pterin ring and suggests a model involving a cationic pterin radical in the catalytic cycle.


==About this Structure==
Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center.,Raman CS, Li H, Martasek P, Kral V, Masters BS, Poulos TL Cell. 1998 Dec 23;95(7):939-50. PMID:9875848<ref>PMID:9875848</ref>
2NSE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with CAC, ZN, ARG, HEM, H4B and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nitric-oxide_synthase Nitric-oxide synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2NSE OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center., Raman CS, Li H, Martasek P, Kral V, Masters BS, Poulos TL, Cell. 1998 Dec 23;95(7):939-50. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9875848 9875848]
</div>
<div class="pdbe-citations 2nse" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Nitric Oxide Synthase|Nitric Oxide Synthase]]
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Nitric-oxide synthase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Nitric Oxide Synthase]]
[[Category: Kral, V.]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Li, H.]]
[[Category: Kral V]]
[[Category: Martasek, P.]]
[[Category: Li H]]
[[Category: Masters, B.S.S.]]
[[Category: Martasek P]]
[[Category: Poulos, T.L.]]
[[Category: Masters BSS]]
[[Category: Raman, C.S.]]
[[Category: Poulos TL]]
[[Category: ARG]]
[[Category: Raman CS]]
[[Category: CAC]]
[[Category: GOL]]
[[Category: H4B]]
[[Category: HEM]]
[[Category: ZN]]
[[Category: arginine]]
[[Category: complex (oxidoreductase/peptide)]]
[[Category: heme protein]]
[[Category: nitric oxide synthase]]
[[Category: tetrahydrobiopterin]]
 
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