4cdt: Difference between revisions
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==Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-((3-Fluorophenethylamino)ethyl)quinolin-2-amine== | ==Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-((3-Fluorophenethylamino)ethyl)quinolin-2-amine== | ||
<StructureSection load='4cdt' size='340' side='right' caption='[[4cdt]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='4cdt' size='340' side='right' caption='[[4cdt]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cam|4cam]], [[4can|4can]], [[4cao|4cao]], [[4cap|4cap]], [[4caq|4caq]], [[4car|4car]], [[4cft|4cft]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cam|4cam]], [[4can|4can]], [[4cao|4cao]], [[4cap|4cap]], [[4caq|4caq]], [[4car|4car]], [[4cft|4cft]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase_(NADPH_dependent) Nitric-oxide synthase (NADPH dependent)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase_(NADPH_dependent) Nitric-oxide synthase (NADPH dependent)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cdt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cdt RCSB], [http://www.ebi.ac.uk/pdbsum/4cdt PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cdt OCA], [http://pdbe.org/4cdt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cdt RCSB], [http://www.ebi.ac.uk/pdbsum/4cdt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cdt ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4cdt" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
Revision as of 13:12, 5 August 2016
Structure of rat neuronal nitric oxide synthase heme domain in complex with 7-((3-Fluorophenethylamino)ethyl)quinolin-2-amineStructure of rat neuronal nitric oxide synthase heme domain in complex with 7-((3-Fluorophenethylamino)ethyl)quinolin-2-amine
Structural highlights
Function[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. Publication Abstract from PubMedSince high levels of nitric oxide (NO) are implicated in neurodegenerative disorders, inhibition of the neuronal isoform of nitric oxide synthase (nNOS) and reduction of NO levels are therapeutically desirable. Nonetheless, many nNOS inhibitors mimic l-arginine and are poorly bioavailable. 2-Aminoquinoline-based scaffolds were designed with the hope that they could (a) mimic aminopyridines as potent, isoform-selective arginine isosteres and (b) possess chemical properties more conducive to oral bioavailability and CNS penetration. A series of these compounds was synthesized and assayed against purified nNOS enzymes, endothelial NOS (eNOS), and inducible NOS (iNOS). Several compounds built on a 7-substituted 2-aminoquinoline core are potent and isoform-selective; X-ray crystallography indicates that aminoquinolines exert inhibitory effects by mimicking substrate interactions with the conserved active site glutamate residue. The most potent and selective compounds, 7 and 15, were tested in a Caco-2 assay and showed good permeability and low efflux, suggesting high potential for oral bioavailability. Simplified 2-Aminoquinoline-Based Scaffold for Potent and Selective Neuronal Nitric Oxide Synthase Inhibition.,Cinelli MA, Li H, Chreifi G, Martasek P, Roman LJ, Poulos TL, Silverman RB J Med Chem. 2014 Feb 10. PMID:24472039[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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