View source for 3rqp


==Structure of the endothelial nitric oxide synthase heme domain in complex with 6-{[(3R,4R)-4-(2-{[(2R/2S)-1-(3-fluorophenyl)propan-2-yl]amino}ethoxy)pyrrolidin-3-yl]methyl}-4-methylpyridin-2-amine==
<StructureSection load='3rqp' size='340' side='right'caption='[[3rqp]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3rqp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RQP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RQP 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]] 2.35&#8491;</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=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=X2E:6-{[(3R,4R)-4-(2-{[(2R)-1-(3-FLUOROPHENYL)PROPAN-2-YL]AMINO}ETHOXY)PYRROLIDIN-3-YL]METHYL}-4-METHYLPYRIDIN-2-AMINE'>X2E</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=3rqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rqp OCA], [https://pdbe.org/3rqp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rqp RCSB], [https://www.ebi.ac.uk/pdbsum/3rqp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rqp 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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Inhibitors of neuronal nitric oxide synthase have been proposed as therapeutics for the treatment of different types of neurological disorders. On the basis of a cis-3,4-pyrrolidine scaffold, a series of trans-cyclopropyl- and methyl-containing nNOS inhibitors have been synthesized. The insertion of a rigid electron-withdrawing cyclopropyl ring decreases the basicity of the adjacent amino group, which resulted in decreased inhibitory activity of these inhibitors compared to the parent compound. Nonetheless, three of them exhibited double-digit nanomolar inhibition with high nNOS selectivity on the basis of in vitro enzyme assays. Crystal structures of nNOS and eNOS with these inhibitors bound provide a basis for detailed structure-activity relationship (SAR) studies. The conclusions from these studies will be used as a guide in the future development of selective NOS inhibitors.

Cyclopropyl- and methyl-containing inhibitors of neuronal nitric oxide synthase.,Li H, Xue F, Kraus JM 2nd, Ji H, Labby KJ, Mataka J, Delker SL, Martasek P, Roman LJ, Poulos TL, Silverman RB Bioorg Med Chem. 2013 Mar 1;21(5):1333-43. doi: 10.1016/j.bmc.2012.12.019. Epub, 2012 Dec 22. PMID:23352768<ref>PMID:23352768</ref>

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

==See Also==
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Large Structures]]
[[Category: Delker SL]]
[[Category: Li H]]
[[Category: Poulos TL]]