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5fvx

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Revision as of 12:38, 16 November 2017

Structure of human nNOS R354A G357D mutant heme domain in complex with with 6-(2-(5-(3-(DIMETHYLAMINO)PROPYL) PYRIDIN-3-YL)ETHYL)-4-METHYLPYRIDIN-2-AMINE

Structural highlights

5fvx is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	5fvo, 5fvp, 5fvq, 5fvr, 5fvs, 5fvt, 5fvu, 5fvv, 5fvw, 5fvy, 5fvz, 5fw0
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.

Publication Abstract from PubMed

Neuronal 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

↑ Wang HY, Qin Y, Li H, Roman LJ, Martasek P, Poulos TL, Silverman RB. Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibition by Optimization of the 2-Aminopyridine-Based Scaffold with a Pyridine Linker. J Med Chem. 2016 Apr 20. PMID:27050842 doi:http://dx.doi.org/10.1021/acs.jmedchem.6b00273

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5fvx"

Categories: Human | Li, H | Poulos, T L | Nitric oxide synthase | Oxidoreductase

@@ Line 3: / Line 3: @@
 <StructureSection load='5fvx' size='340' side='right' caption='[[5fvx]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5fvx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FVX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5fvx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FVX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FVX FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=W67:6-(2-(5-(3-(DIMETHYLAMINO)PROPYL)PYRIDIN-3-YL)ETHYL)-4-METHYLPYRIDIN-2-AMINE'>W67</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]], [[5fvq|5fvq]], [[5fvr|5fvr]], [[5fvs|5fvs]], [[5fvt|5fvt]], [[5fvu|5fvu]], [[5fvv|5fvv]], [[5fvw|5fvw]], [[5fvy|5fvy]], [[5fvz|5fvz]], [[5fw0|5fw0]]</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=5fvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fvx OCA], [http://pdbe.org/5fvx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fvx RCSB], [http://www.ebi.ac.uk/pdbsum/5fvx 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=5fvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fvx OCA], [http://pdbe.org/5fvx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fvx RCSB], [http://www.ebi.ac.uk/pdbsum/5fvx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fvx ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Li, H]]
 [[Category: Poulos, T L]]
 [[Category: Nitric oxide synthase]]
 [[Category: Oxidoreductase]]

5fvx

From Proteopedia

Revision as of 12:38, 16 November 2017

Structure of human nNOS R354A G357D mutant heme domain in complex with with 6-(2-(5-(3-(DIMETHYLAMINO)PROPYL) PYRIDIN-3-YL)ETHYL)-4-METHYLPYRIDIN-2-AMINE

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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