View source for 3dqt


==Structure of endothelial NOS heme domain in complex with a inhibitor (+-)-N1-{trans-4'-[(6"-amino-4"-methylpyridin-2"-yl)methyl]pyrrolidin-3'-yl}-N2-(3'-chlorobenzyl)ethane-1,2-diamine==
<StructureSection load='3dqt' size='340' side='right'caption='[[3dqt]], [[Resolution|resolution]] 2.54&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3dqt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DQT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DQT FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=JI7:N-{(3R,4S)-4-[(6-AMINO-4-METHYLPYRIDIN-2-YL)METHYL]PYRROLIDIN-3-YL}-N-(3-CHLOROBENZYL)ETHANE-1,2-DIAMINE'>JI7</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3b3p|3b3p]], [[3dqs|3dqs]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NOS3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Nitric-oxide_synthase_(NADPH_dependent) Nitric-oxide synthase (NADPH dependent)], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] </span></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=3dqt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dqt OCA], [https://pdbe.org/3dqt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dqt RCSB], [https://www.ebi.ac.uk/pdbsum/3dqt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dqt 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/dq/3dqt_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3dqt ConSurf].
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== Publication Abstract from PubMed ==
New nitric oxide synthase (NOS) inhibitors were designed de novo with knowledge gathered from the studies on the nNOS-selective dipeptide inhibitors. Each of the new inhibitors consists of three fragments: an aminopyridine ring, a pyrrolidine, and a tail of various length and polarity. The in vitro inhibitory assays indicate good potency and isoform selectivity for some of the compounds. Crystal structures of these inhibitors bound to either wild type or mutant nNOS and eNOS have confirmed design expectations. The aminopyridine ring mimics the guanidinium group of l-arginine and functions as an anchor to place the compound in the NOS active site where it hydrogen bonds to a conserved Glu. The rigidity of the pyrrolidine ring places the pyrrolidine ring nitrogen between the same conserved Glu and the selective residue nNOS Asp597/eNOS Asn368, which results in similar interactions observed with the alpha-amino group of dipeptide inhibitors bound to nNOS. These structures provide additional information to help in the design of inhibitors with greater potency, physicochemical properties, and isoform selectivity.

Crystal Structures of Constitutive Nitric Oxide Synthases in Complex with De Novo Designed Inhibitors (dagger).,Igarashi J, Li H, Jamal J, Ji H, Fang J, Lawton GR, Silverman RB, Poulos TL J Med Chem. 2009 Mar 18. PMID:19296678<ref>PMID:19296678</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3dqt" style="background-color:#fffaf0;"></div>

==See Also==
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bovin]]
[[Category: Large Structures]]
[[Category: Igarashi, J]]
[[Category: Li, H]]
[[Category: Poulos, T L]]
[[Category: Blood coagulation]]
[[Category: Calmodulin-binding]]
[[Category: Cytoskeleton]]
[[Category: Fad]]
[[Category: Fmn]]
[[Category: Golgi apparatus]]
[[Category: Heme]]
[[Category: Iron]]
[[Category: Lipoprotein]]
[[Category: Membrane]]
[[Category: Metal-binding]]
[[Category: Myristate]]
[[Category: Nadp]]
[[Category: Nitric oxide synthase heme enzyme inhibitor]]
[[Category: Oxidoreductase]]
[[Category: Palmitate]]
[[Category: Phosphoprotein]]