4ctr: Difference between revisions

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-'''Unreleased structure'''
-The entry 4ctr is ON HOLD  until Paper Publication
+==Structure of rat neuronal nitric oxide synthase heme domain in complex with 2-(6-Amino-4-methylpyridin-2-yl)-1-(3-(2-(6-amino-4- methylpyridin-2-yl)ethyl )phenyl)ethan-1-ol==
+<StructureSection load='4ctr' size='340' side='right'caption='[[4ctr]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4ctr]] 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=4CTR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CTR FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=S20:(1S)-2-(6-AMINO-4-METHYLPYRIDIN-2-YL)-1-{3-[2-(6-AMINO-4-METHYLPYRIDIN-2-YL)ETHYL]PHENYL}ETHANOL'>S20</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4ctr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ctr OCA], [https://pdbe.org/4ctr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ctr RCSB], [https://www.ebi.ac.uk/pdbsum/4ctr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ctr 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.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Overproduction of NO by nNOS is implicated in the pathogenesis of diverse neuronal disorders. Since NO signaling is involved in diverse physiological functions, selective inhibition of nNOS over other isoforms is essential to minimize side effects. A series of alpha-amino functionalized aminopyridine derivatives (3 - 8) were designed to probe the structure-activity relationship between ligand, heme propionate, and H4B. Compound 8R was identified as the most potent and selective molecule of this study, exhibiting a Ki of 24 nM for nNOS, with 273-fold and 2822-fold selectivity against iNOS and eNOS, respectively. Although crystal structures of 8R complexed with nNOS and eNOS revealed a similar binding mode, the selectivity stems from the distinct electrostatic environments in two isoforms that result in much lower inhibitor binding free energy in nNOS than in eNOS. These findings provide a basis for further development of simple, but even more selective and potent, nNOS inhibitors.
-Authors: Li, H., Poulos, T.L.
+Nitric Oxide Synthase Inhibitors that Interact with both a Heme Propionate and Tetrahydrobiopterin Show High Isoform Selectivity.,Kang S, Tang W, Li H, Chreifi G, Martasek P, Roman LJ, Poulos TL, Silverman RB J Med Chem. 2014 Apr 23. PMID:24758147<ref>PMID:24758147</ref>
-Description: Structure of rat neuronal nitric oxide synthase heme domain in complex with 2-(6-Amino-4-methylpyridin-2-yl)-1-(3-(2-(6-amino-4-methylpyridin-2-yl)ethyl )phenyl)ethan-1-ol
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4ctr" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Rattus norvegicus]]
+[[Category: Li H]]
+[[Category: Poulos TL]]