5ad4: Difference between revisions
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<StructureSection load='5ad4' size='340' side='right'caption='[[5ad4]], [[Resolution|resolution]] 1.98Å' scene=''> | <StructureSection load='5ad4' size='340' side='right'caption='[[5ad4]], [[Resolution|resolution]] 1.98Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ad4]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AD4 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5ad4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AD4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AD4 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6M8:7-[[3-[2-(DIMETHYLAMINO)ETHYL]PHENOXY]METHYL]QUINOLIN-2-AMINE'>6M8</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6M8:7-[[3-[2-(DIMETHYLAMINO)ETHYL]PHENOXY]METHYL]QUINOLIN-2-AMINE'>6M8</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=5ad4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ad4 OCA], [https://pdbe.org/5ad4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ad4 RCSB], [https://www.ebi.ac.uk/pdbsum/5ad4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ad4 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/NOS1_RAT NOS1_RAT] 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. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Nitric Oxide Synthase|Nitric Oxide Synthase]] | *[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Rattus norvegicus]] | ||
[[Category: | [[Category: Li H]] | ||
[[Category: | [[Category: Poulos TL]] | ||
Revision as of 07:52, 25 May 2023
Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-((3-(2-(Dimethylamino)ethyl)phenoxy)methyl)quinolin-2- amineStructure of rat neuronal nitric oxide synthase heme domain in complex with 7-((3-(2-(Dimethylamino)ethyl)phenoxy)methyl)quinolin-2- amine
Structural highlights
FunctionNOS1_RAT 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. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Publication Abstract from PubMedExcess nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is implicated in neurodegenerative disorders. As a result, inhibition of nNOS and reduction of NO levels is desirable therapeutically, but many nNOS inhibitors are poorly bioavailable. Promising members of our previously reported 2-aminoquinoline class of nNOS inhibitors, although orally bioavailable and brain-penetrant, suffer from unfavorable off-target binding to other CNS receptors, and they resemble known promiscuous binders. Rearranged phenyl ether- and aniline-linked 2-aminoquinoline derivatives were therefore designed to (a) disrupt the promiscuous binding pharmacophore and diminish off-target interactions and (b) preserve potency, isoform selectivity, and cell permeability. A series of these compounds was synthesized and tested against purified nNOS, endothelial NOS (eNOS), and inducible NOS (iNOS) enzymes. One compound, 20, displayed high potency, selectivity, and good human nNOS inhibition, and retained some permeability in a Caco-2 assay. Most promisingly, CNS receptor counterscreening revealed that this rearranged scaffold significantly reduces off-target binding. Phenyl Ether- and Aniline-Containing 2-Aminoquinolines as Potent and Selective Inhibitors of Neuronal Nitric Oxide Synthase.,Cinelli MA, Li H, Pensa AV, Kang S, Roman LJ, Martasek P, Poulos TL, Silverman RB J Med Chem. 2015 Nov 12;58(21):8694-712. doi: 10.1021/acs.jmedchem.5b01330. Epub , 2015 Oct 27. PMID:26469213[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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