3e7t: Difference between revisions

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{{Seed}}
[[Image:3e7t.jpg|left|200px]]


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==Structure of murine iNOS oxygenase domain with inhibitor AR-C102222==
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<StructureSection load='3e7t' size='340' side='right'caption='[[3e7t]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[3e7t]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. The January 2011 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Nitric Oxide Synthase''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2011_1 10.2210/rcsb_pdb/mom_2011_1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E7T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E7T FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B14:1-(6-CYANO-3-PYRIDYLCARBONYL)-5,8-DIFLUOROSPIRO[PIPERIDINE-4,2(1H)-QUINAZOLINE]-4-AMINE'>B14</scene>, <scene name='pdbligand=HBI:7,8-DIHYDROBIOPTERIN'>HBI</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
{{STRUCTURE_3e7t|  PDB=3e7t  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3e7t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e7t OCA], [https://pdbe.org/3e7t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e7t RCSB], [https://www.ebi.ac.uk/pdbsum/3e7t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e7t ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NOS2_MOUSE NOS2_MOUSE] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2.<ref>PMID:16373578</ref>
== 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/e7/3e7t_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3e7t ConSurf].
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== Publication Abstract from PubMed ==
Nitric 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.


===Structure of murine iNOS oxygenase domain with inhibitor AR-C102222===
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<ref>PMID:18849972</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3e7t" style="background-color:#fffaf0;"></div>


==About this Structure==
==See Also==
3E7T is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E7T OCA].
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Nitric-oxide synthase]]
[[Category: Nitric Oxide Synthase]]
[[Category: Single protein]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Aberg, A.]]
[[Category: Aberg A]]
[[Category: Andersson, G.]]
[[Category: Andersson G]]
[[Category: Andrews, G.]]
[[Category: Andrews G]]
[[Category: Arvai, A S.]]
[[Category: Arvai AS]]
[[Category: Cheshire, D R.]]
[[Category: Cheshire DR]]
[[Category: Connolly, S.]]
[[Category: Connolly S]]
[[Category: Crane, B R.]]
[[Category: Crane BR]]
[[Category: Garcin, E D.]]
[[Category: Garcin ED]]
[[Category: Gensmantel, N P.]]
[[Category: Gensmantel NP]]
[[Category: Getzoff, E D.]]
[[Category: Getzoff ED]]
[[Category: Hamley, P J.]]
[[Category: Hamley PJ]]
[[Category: Kroeger, M D.]]
[[Category: Kroeger MD]]
[[Category: Mallinder, P R.]]
[[Category: Mallinder PR]]
[[Category: Mete, A.]]
[[Category: Mete A]]
[[Category: Nicholls, D J.]]
[[Category: Nicholls DJ]]
[[Category: Rosenfeld, R J.]]
[[Category: Rosenfeld RJ]]
[[Category: St-Gallay, S A.]]
[[Category: St-Gallay SA]]
[[Category: Stuehr, D J.]]
[[Category: Stuehr DJ]]
[[Category: Tainer, J A.]]
[[Category: Tainer JA]]
[[Category: Tinker, A C.]]
[[Category: Tinker AC]]
[[Category: Wallace, A V.]]
[[Category: Wallace AV]]
[[Category: Fad]]
[[Category: Fmn]]
[[Category: Heme]]
[[Category: Iron]]
[[Category: Metal-binding]]
[[Category: Nadp]]
[[Category: Nitric oxide synthase]]
[[Category: No]]
[[Category: Oxidoreductase]]
[[Category: Oxidoreductase calmodulin-binding]]
[[Category: Polymorphism]]
[[Category: Tetrahydrobiopterin]]
[[Category: Zinc]]
 
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