3tyl
From Proteopedia
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| - | [[ | + | ==Structure of neuronal nitric oxide synthase heme domain in complex with 6-(((3S,4S)-4-(2-((2-fluorobenzyl)amino)ethoxy)pyrrolidin-3-yl)methyl)-4-methylpyridin-2-amine== |
| + | <StructureSection load='3tyl' size='340' side='right' caption='[[3tyl]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3tyl]] is a 2 chain structure with sequence 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=3TYL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TYL 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=AXW:6-{[(3S,4S)-4-{2-[(2-FLUOROBENZYL)AMINO]ETHOXY}PYRROLIDIN-3-YL]METHYL}-4-METHYLPYRIDIN-2-AMINE'>AXW</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3tym|3tym]], [[3tyn|3tyn]], [[3tyo|3tyo]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nos1, Bnos ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</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 Nitric-oxide synthase], 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=3tyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tyl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tyl RCSB], [http://www.ebi.ac.uk/pdbsum/3tyl PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Selective neuronal nitric oxide synthase (nNOS) inhibitors have therapeutic applications in the treatment of numerous neurodegenerative diseases. Here we report the synthesis and evaluation of a series of inhibitors designed to have increased cell membrane permeability via intramolecular hydrogen bonding. Their potencies were examined in both purified enzyme and cell-based assays; a comparison of these results demonstrates that two of the new inhibitors display significantly increased membrane permeability over previous analogs. NMR spectroscopy provides evidence of intramolecular hydrogen bonding under physiological conditions in two of the inhibitors. Crystal structures of the inhibitors in the nNOS active site confirm the predicted non-intramolecular hydrogen bonded binding mode. Intramolecular hydrogen bonding may be an effective approach for increasing cell membrane permeability without affecting target protein binding. | ||
| - | + | Intramolecular hydrogen bonding: A potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase.,Labby KJ, Xue F, Kraus JM, Ji H, Mataka J, Li H, Martasek P, Roman LJ, Poulos TL, Silverman RB Bioorg Med Chem. 2012 Feb 7. PMID:22370337<ref>PMID:22370337</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Nitric Oxide Synthase|Nitric Oxide Synthase]] | *[[Nitric Oxide Synthase|Nitric Oxide Synthase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Nitric-oxide synthase]] | [[Category: Nitric-oxide synthase]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
| - | [[Category: Li, H | + | [[Category: Li, H]] |
| - | [[Category: Poulos, T L | + | [[Category: Poulos, T L]] |
[[Category: Inhibitor binding]] | [[Category: Inhibitor binding]] | ||
[[Category: Nitric oxide synthase]] | [[Category: Nitric oxide synthase]] | ||
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | ||
Revision as of 17:42, 9 December 2014
Structure of neuronal nitric oxide synthase heme domain in complex with 6-(((3S,4S)-4-(2-((2-fluorobenzyl)amino)ethoxy)pyrrolidin-3-yl)methyl)-4-methylpyridin-2-amine
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