6pox: Difference between revisions

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'''Unreleased structure'''


The entry 6pox is ON HOLD  until Paper Publication
==Structure of human endothelialnitric oxide synthase heme domain in complex with 7-(3-(Aminomethyl)-4-ethoxyphenyl)-4-methylquinolin-2-amine==
<StructureSection load='6pox' size='340' side='right'caption='[[6pox]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6POX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6POX 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]] 2.197&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GD:GADOLINIUM+ATOM'>GD</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=OSJ:7-[3-(aminomethyl)-4-ethoxyphenyl]-4-methylquinolin-2-amine'>OSJ</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=6pox FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pox OCA], [https://pdbe.org/6pox PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pox RCSB], [https://www.ebi.ac.uk/pdbsum/6pox PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pox ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Inhibition of neuronal nitric oxide synthase (nNOS), an enzyme implicated in neurodegenerative disorders, is an attractive strategy for treating or preventing these diseases. We previously developed several classes of 2-aminoquinoline-based nNOS inhibitors, but these compounds had drawbacks including off-target promiscuity, low activity against human nNOS, and only modest selectivity for nNOS over related enzymes. In this study, we synthesized new nNOS inhibitors based on 7-phenyl-2-aminoquinoline and assayed them against rat and human nNOS, human eNOS, and murine and (in some cases) human iNOS. Compounds with a meta-relationship between the aminoquinoline and a positively charged tail moiety were potent and had up to nearly 900-fold selectivity for human nNOS over human eNOS. X-ray crystallography indicates that the amino groups of some compounds occupy a water-filled pocket surrounding an nNOS-specific aspartate residue (absent in eNOS). This interaction was confirmed by mutagenesis studies, making 7-phenyl-2-aminoquinolines the first aminoquinolines to interact with this residue.


Authors: Chreifi, G., Li, H., Poulos, T.L.
First Contact: 7-Phenyl-2-Aminoquinolines, Potent and Selective Neuronal Nitric Oxide Synthase Inhibitors That Target an Isoform-Specific Aspartate.,Cinelli MA, Reidl CT, Li H, Chreifi G, Poulos TL, Silverman RB J Med Chem. 2020 Apr 17. doi: 10.1021/acs.jmedchem.9b01573. PMID:32302123<ref>PMID:32302123</ref>


Description: Structure of human endothelialnitric oxide synthase heme domain in complex with 7-(3-(Aminomethyl)-4-ethoxyphenyl)-4-methylquinolin-2-amine
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Li, H]]
<div class="pdbe-citations 6pox" style="background-color:#fffaf0;"></div>
[[Category: Chreifi, G]]
 
[[Category: Poulos, T.L]]
==See Also==
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Chreifi G]]
[[Category: Li H]]
[[Category: Poulos TL]]
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