2wu4: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:2wu4.png|left|200px]]
-<!--
+==CRYSTAL STRUCTURE OF MOUSE ACETYLCHOLINESTERASE IN COMPLEX WITH FENAMIPHOS AND ORTHO-7==
-The line below this paragraph, containing "STRUCTURE_2wu4", creates the "Structure Box" on the page.
+<StructureSection load='2wu4' size='340' side='right'caption='[[2wu4]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2wu4]] is a 2 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=2WU4 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>, <scene name='pdbligand=SXE:O-{(S)-ETHOXY[(1-METHYLETHYL)AMINO]PHOSPHORYL}-L-SERINE'>SXE</scene></td></tr>
-{{STRUCTURE_2wu4|  PDB=2wu4  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wu4 OCA], [https://pdbe.org/2wu4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wu4 RCSB], [https://www.ebi.ac.uk/pdbsum/2wu4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wu4 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/ACES_MOUSE ACES_MOUSE] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft.
+== 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/wu/2wu4_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=2wu4 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-===CRYSTAL STRUCTURE OF MOUSE ACETYLCHOLINESTERASE IN COMPLEX WITH FENAMIPHOS AND ORTHO-7===
+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>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2wu4" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_19732756}}, adds the Publication Abstract to the page
+*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 19732756 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_19732756}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Large Structures]]
-WU4 is a 2 chains structure of sequences 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].
-==Reference==
-<ref group="xtra">PMID:19732756</ref><references group="xtra"/>
-[[Category: Acetylcholinesterase]]
 [[Category: Mus musculus]]
-[[Category: Artursson, E.]]
+[[Category: Artursson E]]
-[[Category: Ekstrom, F.]]
+[[Category: Ekstrom F]]
-[[Category: Hornberg, A.]]
+[[Category: Hornberg A]]
-[[Category: Pang, Y P.]]
+[[Category: Pang Y-P]]
-[[Category: Warme, R.]]
+[[Category: Warme R]]
-[[Category: Acetylcholinesterase]]
-[[Category: Alternative splicing]]
-[[Category: Fenamipho]]
-[[Category: Glycoprotein]]
-[[Category: Hydrolase]]
-[[Category: Membrane]]
-[[Category: Neurotransmitter degradation]]
-[[Category: Serine esterase]]
-[[Category: Synapse]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec  9 14:01:16 2009''