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New page: left|200px<br /> <applet load="3nos" size="450" color="white" frame="true" align="right" spinBox="true" caption="3nos, resolution 2.400Å" /> '''HUMAN ENDOTHELIAL ...
 
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[[Image:3nos.gif|left|200px]]<br />
<applet load="3nos" size="450" color="white" frame="true" align="right" spinBox="true"
caption="3nos, resolution 2.400&Aring;" />
'''HUMAN ENDOTHELIAL NITRIC OXIDE SYNTHASE WITH ARGININE SUBSTRATE'''<br />


==Overview==
==HUMAN ENDOTHELIAL NITRIC OXIDE SYNTHASE WITH ARGININE SUBSTRATE==
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.
<StructureSection load='3nos' size='340' side='right'caption='[[3nos]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3nos]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NOS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NOS 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HAR:N-OMEGA-HYDROXY-L-ARGININE'>HAR</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=3nos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nos OCA], [https://pdbe.org/3nos PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nos RCSB], [https://www.ebi.ac.uk/pdbsum/3nos PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nos ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NOS3_HUMAN 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.<ref>PMID:17264164</ref>  Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.<ref>PMID:17264164</ref>
== 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/no/3nos_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=3nos ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.


==Disease==
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<ref>PMID:10074942</ref>
Known diseases associated with this structure: Alzheimer disease, late-onset, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163729 163729]], Coronary spasms, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163729 163729]], Hypertension, pregnancy-induced OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163729 163729]], Hypertension, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163729 163729]], Placental abruption OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=163729 163729]]


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
3NOS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, HAR, HEM and H4B 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=3NOS OCA].
</div>
<div class="pdbe-citations 3nos" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10074942 10074942]
*[[Nitric Oxide Synthase|Nitric Oxide Synthase]]
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Nitric-oxide synthase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Fischmann TO]]
[[Category: Fischmann, T.O.]]
[[Category: Weber PC]]
[[Category: Weber, P.C.]]
[[Category: H4B]]
[[Category: HAR]]
[[Category: HEM]]
[[Category: ZN]]
[[Category: human]]
[[Category: l-arginine monooxygenase]]
[[Category: nitric oxide]]
[[Category: zns4]]
 
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