3nnz: Difference between revisions

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-{{Seed}}
-[[Image:3nnz.jpg|left|200px]]
-<!--
+==Structure of rat neuronal nitric oxide synthase heme domain complexed with 6-(((3S,4S)-4-(2-(3-Fluorophenethylamino)ethoxy)pyrrolidin-3-yl)methyl)pyridin-2-amine==
-The line below this paragraph, containing "STRUCTURE_3nnz", creates the "Structure Box" on the page.
+<StructureSection load='3nnz' size='340' side='right'caption='[[3nnz]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3nnz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NNZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NNZ FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.97&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=59W:6-{[(3S,4S)-4-(2-{[2-(3-FLUOROPHENYL)ETHYL]AMINO}ETHOXY)PYRROLIDIN-3-YL]METHYL}PYRIDIN-2-AMINE'>59W</scene>, <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=ZN:ZINC+ION'>ZN</scene></td></tr>
-{{STRUCTURE_3nnz|  PDB=3nnz  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3nnz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nnz OCA], [https://pdbe.org/3nnz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nnz RCSB], [https://www.ebi.ac.uk/pdbsum/3nnz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nnz ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/NOS1_RAT 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.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nn/3nnz_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3nnz ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Selective inhibition of the neuronal isoform of nitric oxide synthase (nNOS) over endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) has become a promising strategy for the discovery of new therapeutic agents for neurodegenerative diseases. However, because of the high sequence homology of different isozymes in the substrate binding pocket, developing inhibitors with both potency and excellent isoform selectivity remains a challenging problem. Herein, we report the evaluation of a recently discovered peripheral hydrophobic pocket (Tyr(706), Leu(337), and Met(336)) that opens up upon inhibitor binding and its potential in designing potent and selective nNOS inhibitors using three compounds, 2a, 2b, and 3. Crystal structure results show that inhibitors 2a and 3 adopted the same binding mode as lead compound 1. We also found that hydrophobic interactions between the 4-methyl group of the aminopyridine ring of these compounds with the side chain of Met(336), as well as the pi-pi stacking interaction between the pyridinyl motif and the side chain of Tyr(706) are important for the high potency and selectivity of these nNOS inhibitors.
-===Structure of rat neuronal nitric oxide synthase heme domain complexed with 6-(((3S,4S)-4-(2-(3-Fluorophenethylamino)ethoxy)pyrrolidin-3-yl)methyl)pyridin-2-amine===
+Peripheral but crucial: A hydrophobic pocket (Tyr706, Leu(337), and Met(336)) for potent and selective inhibition of neuronal nitric oxide synthase.,Xue F, Li H, Fang J, Roman LJ, Martasek P, Poulos TL, Silverman RB Bioorg Med Chem Lett. 2010 Aug 26. PMID:20833542<ref>PMID:20833542</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3nnz" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_20833542}}, adds the Publication Abstract to the page
+*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 20833542 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_20833542}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Large Structures]]
-NNZ is a 2 chains structure with sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NNZ OCA].
-==Reference==
-<ref group="xtra">PMID:20833542</ref><references group="xtra"/>
-[[Category: Nitric-oxide synthase]]
 [[Category: Rattus norvegicus]]
-[[Category: Li, H.]]
+[[Category: Li H]]
-[[Category: Poulos, T L.]]
+[[Category: Poulos TL]]
-[[Category: Heme enzyme]]
-[[Category: Inhibitor]]
-[[Category: Nitric oxide synthase]]
-[[Category: Oxidoreductase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct  6 06:06:57 2010''