5uo4

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (14:28, 6 March 2024) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
==Structure of human neuronal nitric oxide synthase heme domain in complex with 3-[(2-amino-4-methylquinolin-7-yl)methoxy]-5-(2-(methylamino)ethyl)benzonitrile==
==Structure of human neuronal nitric oxide synthase heme domain in complex with 3-[(2-amino-4-methylquinolin-7-yl)methoxy]-5-(2-(methylamino)ethyl)benzonitrile==
-
<StructureSection load='5uo4' size='340' side='right' caption='[[5uo4]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+
<StructureSection load='5uo4' size='340' side='right'caption='[[5uo4]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[5uo4]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UO4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UO4 FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[5uo4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UO4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UO4 FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8F1:3-[(2-AMINO-4-METHYLQUINOLIN-7-YL)METHOXY]-5-[2-(METHYLAMINO)ETHYL]BENZONITRILE'>8F1</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5unr|5unr]], [[5unu|5unu]], [[5unx|5unx]], [[5unw|5unw]], [[5uo1|5uo1]], [[5uny|5uny]], [[5uo3|5uo3]], [[5uo5|5uo5]], [[5uo6|5uo6]], [[5uo7|5uo7]], [[5uo8|5uo8]], [[5uo2|5uo2]], [[5uns|5uns]], [[5unz|5unz]], [[5uo0|5uo0]], [[5unt|5unt]], [[5unv|5unv]], [[5uod|5uod]], [[5uo9|5uo9]], [[5uoa|5uoa]], [[5uob|5uob]], [[5uoc|5uoc]]</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8F1:3-[(2-AMINO-4-METHYLQUINOLIN-7-YL)METHOXY]-5-[2-(METHYLAMINO)ETHYL]BENZONITRILE'>8F1</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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='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'>[https://proteopedia.org/fgij/fg.htm?mol=5uo4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uo4 OCA], [https://pdbe.org/5uo4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uo4 RCSB], [https://www.ebi.ac.uk/pdbsum/5uo4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uo4 ProSAT]</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=5uo4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uo4 OCA], [http://pdbe.org/5uo4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uo4 RCSB], [http://www.ebi.ac.uk/pdbsum/5uo4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uo4 ProSAT]</span></td></tr>
+
</table>
</table>
== Function ==
== Function ==
-
[[http://www.uniprot.org/uniprot/NOS1_HUMAN 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.
+
[https://www.uniprot.org/uniprot/NOS1_HUMAN 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.
-
<div style="background-color:#fffaf0;">
+
-
== Publication Abstract from PubMed ==
+
-
Neuronal nitric oxide synthase (nNOS) inhibition is a promising strategy to treat neurodegenerative disorders, but the development of nNOS inhibitors is often hindered by poor pharmacokinetics. We previously developed a class of membrane-permeable 2-aminoquinoline inhibitors and later rearranged the scaffold to decrease off-target binding. However, the resulting compounds had decreased permeability, low human nNOS activity, and low selectivity versus human eNOS. In this study, 5-substituted phenyl ether-linked aminoquinolines and derivatives were synthesized and assayed against purified NOS isoforms. 5-Cyano compounds are especially potent and selective rat and human nNOS inhibitors. Activity and selectivity are mediated by the binding of the cyano group to a new auxiliary pocket in nNOS. Potency was enhanced by methylation of the quinoline and by introduction of simple chiral moieties, resulting in a combination of hydrophobic and auxiliary pocket effects that yielded high ( approximately 500-fold) n/e selectivity. Importantly, the Caco-2 assay also revealed improved membrane permeability over previous compounds.
+
-
Nitrile in the Hole: Discovery of a Small Auxiliary Pocket in Neuronal Nitric Oxide Synthase Leading to the Development of Potent and Selective 2-Aminoquinoline Inhibitors.,Cinelli MA, Li H, Chreifi G, Poulos TL, Silverman RB J Med Chem. 2017 Apr 19. doi: 10.1021/acs.jmedchem.7b00259. PMID:28422508<ref>PMID:28422508</ref>
+
==See Also==
-
 
+
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 5uo4" style="background-color:#fffaf0;"></div>
+
-
== References ==
+
-
<references/>
+
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Li, H]]
+
[[Category: Homo sapiens]]
-
[[Category: Poulos, T L]]
+
[[Category: Large Structures]]
-
[[Category: Complex]]
+
[[Category: Li H]]
-
[[Category: Enzyme]]
+
[[Category: Poulos TL]]
-
[[Category: Heme]]
+
-
[[Category: Inhibitor]]
+
-
[[Category: Nitric]]
+
-
[[Category: Oxide]]
+
-
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
+
-
[[Category: Synthase]]
+

Current revision

Structure of human neuronal nitric oxide synthase heme domain in complex with 3-[(2-amino-4-methylquinolin-7-yl)methoxy]-5-(2-(methylamino)ethyl)benzonitrile

PDB ID 5uo4

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5uo4"
Personal tools