3jwu
From Proteopedia
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| - | [[Image:3jwu.png|left|200px]] | ||
| - | { | + | ==Structure of rat neuronal nitric oxide synthase R349A mutant heme domain in complex with N1-{(3'R,4'S)-4'-[(6"-amino-4"-methylpyridin-2"-yl)methyl]pyrrolidin-3'-yl}-N2-(3'-fluorophenethyl)ethane-1,2-diamine tetrahydrochloride== |
| + | <StructureSection load='3jwu' size='340' side='right'caption='[[3jwu]], [[Resolution|resolution]] 1.93Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3jwu]] 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=3JWU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JWU 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]] 1.93Å</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=J11:N-{(3R,4S)-4-[(6-AMINO-4-METHYLPYRIDIN-2-YL)METHYL]PYRROLIDIN-3-YL}-N-[2-(3-FLUOROPHENYL)ETHYL]ETHANE-1,2-DIAMINE'>J11</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=3jwu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jwu OCA], [https://pdbe.org/3jwu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jwu RCSB], [https://www.ebi.ac.uk/pdbsum/3jwu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jwu 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/jw/3jwu_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=3jwu 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 NOS (nNOS) has been shown to prevent brain injury and is important for the treatment of various neurodegenerative disorders. However, given the high active site conservation among all three NOS isoforms, the design of selective inhibitors is an extremely challenging problem. Here we present the structural basis for why novel and potent nNOS inhibitors exhibit the highest level of selectivity over eNOS reported so far (approximately 3,800-fold). By using a combination of crystallography, computational methods, and site-directed mutagenesis, we found that inhibitor chirality and an unanticipated structural change of the target enzyme control both the orientation and selectivity of these novel nNOS inhibitors. A new hot spot generated as a result of enzyme elasticity provides important information for the future fragment-based design of selective NOS inhibitors. | ||
| - | + | Unexpected binding modes of nitric oxide synthase inhibitors effective in the prevention of a cerebral palsy phenotype in an animal model.,Delker SL, Ji H, Li H, Jamal J, Fang J, Xue F, Silverman RB, Poulos TL J Am Chem Soc. 2010 Apr 21;132(15):5437-42. PMID:20337441<ref>PMID:20337441</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 3jwu" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
| - | *[[Nitric Oxide Synthase|Nitric Oxide Synthase]] | + | *[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| + | [[Category: Large Structures]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
| - | [[Category: Delker | + | [[Category: Delker SL]] |
| - | [[Category: Li | + | [[Category: Li H]] |
| - | [[Category: Poulos | + | [[Category: Poulos TL]] |
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| - | + | ||
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Current revision
Structure of rat neuronal nitric oxide synthase R349A mutant heme domain in complex with N1-{(3'R,4'S)-4'-[(6"-amino-4"-methylpyridin-2"-yl)methyl]pyrrolidin-3'-yl}-N2-(3'-fluorophenethyl)ethane-1,2-diamine tetrahydrochloride
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