3e7s: Difference between revisions
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<StructureSection load='3e7s' size='340' side='right'caption='[[3e7s]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='3e7s' size='340' side='right'caption='[[3e7s]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3e7s]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3e7s]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E7S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E7S FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AT2:ETHYL+4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE'>AT2</scene>, <scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene>, <scene name='pdbligand=HEC:HEME+C'>HEC</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=3e7s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e7s OCA], [https://pdbe.org/3e7s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e7s RCSB], [https://www.ebi.ac.uk/pdbsum/3e7s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e7s ProSAT]</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=3e7s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e7s OCA], [https://pdbe.org/3e7s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e7s RCSB], [https://www.ebi.ac.uk/pdbsum/3e7s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e7s ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/NOS3_BOVIN NOS3_BOVIN] Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
| Line 18: | Line 15: | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e7/3e7s_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e7/3e7s_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/ | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
| Line 39: | Line 36: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Bos taurus]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Aberg | [[Category: Aberg A]] | ||
[[Category: Andersson | [[Category: Andersson G]] | ||
[[Category: Andrews | [[Category: Andrews G]] | ||
[[Category: Arvai | [[Category: Arvai AS]] | ||
[[Category: Cheshire | [[Category: Cheshire DR]] | ||
[[Category: Connolly | [[Category: Connolly S]] | ||
[[Category: Crane | [[Category: Crane BR]] | ||
[[Category: Garcin | [[Category: Garcin ED]] | ||
[[Category: Gensmantel | [[Category: Gensmantel NP]] | ||
[[Category: Getzoff | [[Category: Getzoff ED]] | ||
[[Category: Hamley | [[Category: Hamley PJ]] | ||
[[Category: Kroeger | [[Category: Kroeger MD]] | ||
[[Category: Mallinder | [[Category: Mallinder PR]] | ||
[[Category: Mete | [[Category: Mete A]] | ||
[[Category: Nicholls | [[Category: Nicholls DJ]] | ||
[[Category: Rosenfeld | [[Category: Rosenfeld RJ]] | ||
[[Category: St-Gallay | [[Category: St-Gallay SA]] | ||
[[Category: Stuehr | [[Category: Stuehr DJ]] | ||
[[Category: Tainer | [[Category: Tainer JA]] | ||
[[Category: Tinker | [[Category: Tinker AC]] | ||
[[Category: Wallace | [[Category: Wallace AV]] | ||
Latest revision as of 12:49, 6 November 2024
Structure of bovine eNOS oxygenase domain with inhibitor AR-C95791Structure of bovine eNOS oxygenase domain with inhibitor AR-C95791
Structural highlights
FunctionNOS3_BOVIN Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedNitric oxide synthase (NOS) enzymes synthesize nitric oxide, a signal for vasodilatation and neurotransmission at low concentrations and a defensive cytotoxin at higher concentrations. The high active site conservation among all three NOS isozymes hinders the design of selective NOS inhibitors to treat inflammation, arthritis, stroke, septic shock and cancer. Our crystal structures and mutagenesis results identified an isozyme-specific induced-fit binding mode linking a cascade of conformational changes to a new specificity pocket. Plasticity of an isozyme-specific triad of distant second- and third-shell residues modulates conformational changes of invariant first-shell residues to determine inhibitor selectivity. To design potent and selective NOS inhibitors, we developed the anchored plasticity approach: anchor an inhibitor core in a conserved binding pocket, then extend rigid bulky substituents toward remote specificity pockets, which become accessible upon conformational changes of flexible residues. This approach exemplifies general principles for the design of selective enzyme inhibitors that overcome strong active site conservation. Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase.,Garcin ED, Arvai AS, Rosenfeld RJ, Kroeger MD, Crane BR, Andersson G, Andrews G, Hamley PJ, Mallinder PR, Nicholls DJ, St-Gallay SA, Tinker AC, Gensmantel NP, Mete A, Cheshire DR, Connolly S, Stuehr DJ, Aberg A, Wallace AV, Tainer JA, Getzoff ED Nat Chem Biol. 2008 Nov;4(11):700-7. Epub 2008 Oct 12. PMID:18849972[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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