5fvq: Difference between revisions
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<StructureSection load='5fvq' size='340' side='right' caption='[[5fvq]], [[Resolution|resolution]] 1.95Å' scene=''> | <StructureSection load='5fvq' size='340' side='right' caption='[[5fvq]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5fvq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FVQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FVQ FirstGlance]. <br> | <table><tr><td colspan='2'>[[5fvq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FVQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FVQ FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=W64:4-METHYL-6-(2-(5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)ETHYL)PYRIDIN-2-AMINE'>W64</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=W64:4-METHYL-6-(2-(5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)ETHYL)PYRIDIN-2-AMINE'>W64</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fvo|5fvo]], [[5fvp|5fvp]], [[5fvr|5fvr]], [[5fvs|5fvs]], [[5fvt|5fvt]], [[5fvu|5fvu]], [[5fvv|5fvv]], [[5fvw|5fvw]], [[5fvx|5fvx]], [[5fvy|5fvy]], [[5fvz|5fvz]], [[5fw0|5fw0]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fvo|5fvo]], [[5fvp|5fvp]], [[5fvr|5fvr]], [[5fvs|5fvs]], [[5fvt|5fvt]], [[5fvu|5fvu]], [[5fvv|5fvv]], [[5fvw|5fvw]], [[5fvx|5fvx]], [[5fvy|5fvy]], [[5fvz|5fvz]], [[5fw0|5fw0]]</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=5fvq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fvq OCA], [http://pdbe.org/5fvq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fvq RCSB], [http://www.ebi.ac.uk/pdbsum/5fvq 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=5fvq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fvq OCA], [http://pdbe.org/5fvq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fvq RCSB], [http://www.ebi.ac.uk/pdbsum/5fvq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fvq ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Buffalo rat]] | |||
[[Category: Li, H]] | [[Category: Li, H]] | ||
[[Category: Poulos, T L]] | [[Category: Poulos, T L]] | ||
Revision as of 15:37, 16 November 2017
Structure of rat neuronal nitric oxide synthase heme domain in complex with 4-methyl-6-(2-(5-(4-methylpiperazin-1-yl)pyridin-3-yl) ethyl)pyridin-2-amineStructure of rat neuronal nitric oxide synthase heme domain in complex with 4-methyl-6-(2-(5-(4-methylpiperazin-1-yl)pyridin-3-yl) ethyl)pyridin-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 PubMedNeuronal nitric oxide synthase (nNOS) is an important therapeutic target for the treatment of various neurodegenerative disorders. A major challenge in the design of nNOS inhibitors focuses on potency in humans and selectivity over other NOS isoforms. Here we report potent and selective human nNOS inhibitors based on the 2-aminopyridine scaffold with a central pyridine linker. Compound 14j, the most promising inhibitor in this study, exhibits excellent potency for rat nNOS (Ki = 16 nM) with 828-fold n/e and 118-fold n/i selectivity with a Ki value of 13 nM against human nNOS with 1761-fold human n/e selectivity. Compound 14j also displayed good metabolic stability in human liver microsomes, low plasma protein binding, and minimal binding to cytochromes P450 (CYPs), although it had little to no Caco-2 permeability. Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibition by Optimization of the 2-Aminopyridine-Based Scaffold with a Pyridine Linker.,Wang HY, Qin Y, Li H, Roman LJ, Martasek P, Poulos TL, Silverman RB J Med Chem. 2016 Apr 20. PMID:27050842[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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