5uo7: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5uo7 is ON HOLD  until Paper Publication
+==Structure of human neuronal nitric oxide synthase heme domain in complex with (S)-3-[(2-amino-4-methylquinolin-7-yl)methoxy]-5-(2-(methylamino)propyl)benzonitrile==
+<StructureSection load='5uo7' size='340' side='right'caption='[[5uo7]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5uo7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UO7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UO7 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]] 2.06&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8FD:3-[(2-AMINO-4-METHYLQUINOLIN-7-YL)METHOXY]-5-[(2S)-2-(METHYLAMINO)PROPYL]BENZONITRILE'>8FD</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5uo7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uo7 OCA], [https://pdbe.org/5uo7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uo7 RCSB], [https://www.ebi.ac.uk/pdbsum/5uo7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uo7 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/NOS1_HUMAN NOS1_HUMAN] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Neuronal nitric oxide synthase (nNOS) inhibition is a promising strategy to treat neurodegenerative disorders, but the development of nNOS inhibitors is often hindered by poor pharmacokinetics. We previously developed a class of membrane-permeable 2-aminoquinoline inhibitors and later rearranged the scaffold to decrease off-target binding. However, the resulting compounds had decreased permeability, low human nNOS activity, and low selectivity versus human eNOS. In this study, 5-substituted phenyl ether-linked aminoquinolines and derivatives were synthesized and assayed against purified NOS isoforms. 5-Cyano compounds are especially potent and selective rat and human nNOS inhibitors. Activity and selectivity are mediated by the binding of the cyano group to a new auxiliary pocket in nNOS. Potency was enhanced by methylation of the quinoline and by introduction of simple chiral moieties, resulting in a combination of hydrophobic and auxiliary pocket effects that yielded high ( approximately 500-fold) n/e selectivity. Importantly, the Caco-2 assay also revealed improved membrane permeability over previous compounds.
-Authors: Li, H., Poulos, T.L.
+Nitrile in the Hole: Discovery of a Small Auxiliary Pocket in Neuronal Nitric Oxide Synthase Leading to the Development of Potent and Selective 2-Aminoquinoline Inhibitors.,Cinelli MA, Li H, Chreifi G, Poulos TL, Silverman RB J Med Chem. 2017 Apr 19. doi: 10.1021/acs.jmedchem.7b00259. PMID:28422508<ref>PMID:28422508</ref>
-Description: Structure of human neuronal nitric oxide synthase heme domain in complex with (S)-3-[(2-amino-4-methylquinolin-7-yl)methoxy]-5-(2-(methylamino)propyl)benzonitrile
+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 5uo7" style="background-color:#fffaf0;"></div>
-[[Category: Poulos, T.L]]
+==See Also==
+*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Li H]]
+[[Category: Poulos TL]]