5vv7: Difference between revisions
New page: ==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 7-(((3-(Pyridin-3-yl)propyl)amino)methyl)quinolin-2-amine== <StructureSection load='5vv7' size='340' si... |
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==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 7-(((3-(Pyridin-3-yl)propyl)amino)methyl)quinolin-2-amine== | ==Structure of bovine endothelial nitric oxide synthase heme domain in complex with 7-(((3-(Pyridin-3-yl)propyl)amino)methyl)quinolin-2-amine== | ||
<StructureSection load='5vv7' size='340' side='right' caption='[[5vv7]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='5vv7' size='340' side='right'caption='[[5vv7]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5vv7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VV7 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5vv7]] 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=5VV7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VV7 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=XH8:7-(((3-(PYRIDIN-3-YL)PROPYL)AMINO)METHYL)QUINOLIN-2-'>XH8</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</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=XH8:7-(((3-(PYRIDIN-3-YL)PROPYL)AMINO)METHYL)QUINOLIN-2-'>XH8</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=5vv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vv7 OCA], [https://pdbe.org/5vv7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vv7 RCSB], [https://www.ebi.ac.uk/pdbsum/5vv7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vv7 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 20: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 5vv7" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5vv7" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Bos taurus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Li H]] | ||
[[Category: | [[Category: Poulos TL]] | ||
Latest revision as of 16:59, 4 October 2023
Structure of bovine endothelial nitric oxide synthase heme domain in complex with 7-(((3-(Pyridin-3-yl)propyl)amino)methyl)quinolin-2-amineStructure of bovine endothelial nitric oxide synthase heme domain in complex with 7-(((3-(Pyridin-3-yl)propyl)amino)methyl)quinolin-2-amine
Structural highlights
FunctionNOS3_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. Publication Abstract from PubMedNeuronal nitric oxide synthase (nNOS) is a target for development of antineurodegenerative agents. Most nNOS inhibitors mimic l-arginine and have poor bioavailability. 2-Aminoquinolines showed promise as bioavailable nNOS inhibitors but suffered from low human nNOS inhibition, low selectivity versus human eNOS, and significant binding to other CNS targets. We aimed to improve human nNOS potency and selectivity and reduce off-target binding by (a) truncating the original scaffold or (b) introducing a hydrophilic group to interrupt the lipophilic, promiscuous pharmacophore and promote interaction with human nNOS-specific His342. We synthesized both truncated and polar 2-aminoquinoline derivatives and assayed them against recombinant NOS enzymes. Although aniline and pyridine derivatives interact with His342, benzonitriles conferred the best rat and human nNOS inhibition. Both introduction of a hydrophobic substituent next to the cyano group and aminoquinoline methylation considerably improved isoform selectivity. Most importantly, these modifications preserved Caco-2 permeability and reduced off-target CNS binding. Hydrophilic, Potent, and Selective 7-Substituted 2-Aminoquinolines as Improved Human Neuronal Nitric Oxide Synthase Inhibitors.,Pensa AV, Cinelli MA, Li H, Chreifi G, Mukherjee P, Roman LJ, Martasek P, Poulos TL, Silverman RB J Med Chem. 2017 Aug 4. doi: 10.1021/acs.jmedchem.7b00835. PMID:28776992[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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