View source for 3pnh


==Structure of Bovine Endothelial Nitric Oxide Synthase Heme Domain in complex with 6-(((3R,4R)-4-(2-((2-FLUORO-2-(3-FLUOROPHENYL) ETHYL)AMINO)ETHOXY)PYRROLIDIN-3-YL)METHYL)-4-METHYLPYRIDIN-2-AMINE==
<StructureSection load='3pnh' size='340' side='right' caption='[[3pnh]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3pnh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PNH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PNH FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8CX:6-{[(3R,4R)-4-(2-{[(2R)-2-FLUORO-2-(3-FLUOROPHENYL)ETHYL]AMINO}ETHOXY)PYRROLIDIN-3-YL]METHYL}-4-METHYLPYRIDIN-2-AMINE'>8CX</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CAD:CACODYLIC+ACID'>CAD</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pne|3pne]], [[3pnf|3pnf]], [[3png|3png]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NOS3 ([http://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'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase_(NADPH_dependent) Nitric-oxide synthase (NADPH dependent)], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3pnh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pnh OCA], [http://pdbe.org/3pnh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3pnh RCSB], [http://www.ebi.ac.uk/pdbsum/3pnh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3pnh ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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. 
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== Publication Abstract from PubMed ==
We report an efficient synthetic route to chiral pyrrolidine inhibitors of neuronal nitric oxide synthase (nNOS) and crystal structures of the inhibitors bound to nNOS and to endothelial NOS. The new route enables versatile structure-activity relationship studies on the pyrrolidine-based scaffold, which can be beneficial for further development of nNOS inhibitors. The X-ray crystal structures of five new fluorine-containing inhibitors bound to nNOS provide insights into the effect of the fluorine atoms on binding.

Improved Synthesis of Chiral Pyrrolidine Inhibitors and Their Binding Properties to Neuronal Nitric Oxide Synthase.,Xue F, Kraus JM, Labby KJ, Ji H, Mataka J, Xia G, Li H, Delker SL, Roman LJ, Martasek P, Poulos TL, Silverman RB J Med Chem. 2011 Sep 22;54(18):6399-6403. Epub 2011 Aug 22. PMID:21809851<ref>PMID:21809851</ref>

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

==See Also==
*[[Nitric Oxide Synthase|Nitric Oxide Synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bovin]]
[[Category: Delker, S L]]
[[Category: Li, H]]
[[Category: Poulos, T L]]
[[Category: Heme enzyme]]
[[Category: Inhibitor]]
[[Category: Oxidoreductase-inhibitor complex]]