2wu4

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[[Image:2wu4.png|left|200px]]
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==CRYSTAL STRUCTURE OF MOUSE ACETYLCHOLINESTERASE IN COMPLEX WITH FENAMIPHOS AND ORTHO-7==
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<StructureSection load='2wu4' size='340' side='right' caption='[[2wu4]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2wu4]] is a 2 chain structure with 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=2WU4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WU4 FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HBP:1,7-HEPTYLENE-BIS-N,N-SYN-2-PYRIDINIUMALDOXIME'>HBP</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene><br>
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<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SXE:O-{(S)-ETHOXY[(1-METHYLETHYL)AMINO]PHOSPHORYL}-L-SERINE'>SXE</scene></td></tr>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2jgh|2jgh]], [[2whq|2whq]], [[1mah|1mah]], [[2ha6|2ha6]], [[1maa|1maa]], [[2c0q|2c0q]], [[2jgg|2jgg]], [[2jgl|2jgl]], [[1q84|1q84]], [[2jgm|2jgm]], [[2jge|2jge]], [[1q83|1q83]], [[2wls|2wls]], [[1c2b|1c2b]], [[2ha3|2ha3]], [[2ha0|2ha0]], [[2jey|2jey]], [[2jgi|2jgi]], [[1n5r|1n5r]], [[2jgj|2jgj]], [[1j06|1j06]], [[2jf0|2jf0]], [[2c0p|2c0p]], [[2h9y|2h9y]], [[2whr|2whr]], [[1n5m|1n5m]], [[2ha5|2ha5]], [[2ha2|2ha2]], [[2whp|2whp]], [[2jez|2jez]], [[2jgk|2jgk]], [[1ku6|1ku6]], [[2ha4|2ha4]], [[1j07|1j07]], [[2jgf|2jgf]], [[2ha7|2ha7]], [[1c2o|1c2o]], [[2wu3|2wu3]]</td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.7 3.1.1.7] </span></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2wu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wu4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wu4 RCSB], [http://www.ebi.ac.uk/pdbsum/2wu4 PDBsum]</span></td></tr>
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<table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wu/2wu4_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Organophosphorus insecticides and nerve agents inhibit the vital enzyme acetylcholinesterase by covalently bonding to the catalytic serine residue of the enzyme. Oxime-based reactivators, such as [(E)-[1-[(4-carbamoylpyridin-1-ium-1-yl)methoxymethyl]pyridin-2-ylidene]me thyl]-oxoazanium dichloride (HI-6) and 1,7-heptylene-bis-N,N'-2-pyridiniumaldoxime dichloride (Ortho-7), restore the organophosphate-inhibited enzymatic activity by cleaving the phosphorous conjugate. In this article, we report the intermolecular interactions between Mus musculus acetylcholinesterase inhibited by the insecticide fenamiphos (fep-mAChE) and HI-6 or Ortho-7 revealed by a combination of crystallography and kinetics. The crystal structures of the two oxime-bound fep-mAChE complexes show that both oximes interact with the peripheral anionic site involving different conformations of Trp286 and different peripheral-site residues (Tyr124 for HI-6 and Tyr72 for Ortho-7). Moreover, residues at catalytic site of the HI-6-bound fep-mAChE complex adopt conformations that are similar to those in the apo mAChE, whereas significant conformational changes are observed for the corresponding residues in the Ortho-7-bound fep-mAChE complex. Interestingly, flipping of the His447 imidazole ring allows the formation of a hydrogen bonding network among the Glu334-His447-Ortho-7 triad, which presumably deprotonates the Ortho-7 oxime hydroxyl group, increases the nucleophilicity of the oxime group, and leads to cleavage of the phosphorous conjugate. These results offer insights into a detailed reactivation mechanism for the oximes and development of improved reactivators.
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{{STRUCTURE_2wu4| PDB=2wu4 | SCENE= }}
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Crystal structures of oxime-bound fenamiphos-acetylcholinesterases: reactivation involving flipping of the His447 ring to form a reactive Glu334-His447-oxime triad.,Hornberg A, Artursson E, Warme R, Pang YP, Ekstrom F Biochem Pharmacol. 2010 Feb 1;79(3):507-15. Epub 2009 Sep 2. PMID:19732756<ref>PMID:19732756</ref>
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===CRYSTAL STRUCTURE OF MOUSE ACETYLCHOLINESTERASE IN COMPLEX WITH FENAMIPHOS AND ORTHO-7===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_19732756}}
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==About this Structure==
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[[2wu4]] is a 2 chain structure with 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=2WU4 OCA].
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==See Also==
==See Also==
*[[Acetylcholinesterase|Acetylcholinesterase]]
*[[Acetylcholinesterase|Acetylcholinesterase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019732756</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Acetylcholinesterase]]
[[Category: Acetylcholinesterase]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]

Revision as of 10:27, 29 September 2014

CRYSTAL STRUCTURE OF MOUSE ACETYLCHOLINESTERASE IN COMPLEX WITH FENAMIPHOS AND ORTHO-7

2wu4, resolution 2.40Å

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