5fvq

From Proteopedia

(Difference between revisions)

Revision as of 12:37, 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-amine

Structural highlights

5fvq is a 2 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	5fvo, 5fvp, 5fvr, 5fvs, 5fvt, 5fvu, 5fvv, 5fvw, 5fvx, 5fvy, 5fvz, 5fw0
Activity:	Nitric-oxide synthase (NADPH dependent), with EC number 1.14.13.39
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 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/5fvq"

@@ Line 3: / Line 3: @@
 <StructureSection load='5fvq' size='340' side='right' caption='[[5fvq]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
 == 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>
 <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='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>
 == Function ==
@@ Line 24: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Buffalo rat]]
 [[Category: Li, H]]
 [[Category: Poulos, T L]]

5fvq

From Proteopedia

Revision as of 12:37, 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-amine

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox