View source for 5bwb


==ACETYLCHOLINESTERASE (E.C. 3.1.1.7) FROM TORPEDO CALIFORNICA IN COMPLEX WITH THE BIS-IMIDAZOLIUM OXIME 2BIM-7==
<StructureSection load='5bwb' size='340' side='right'caption='[[5bwb]], [[Resolution|resolution]] 2.57&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5bwb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Tetronarce_californica Tetronarce californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BWB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BWB 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]] 2.57&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4VV:(Z,Z)-[HEPTANE-1,7-DIYLBIS(1H-IMIDAZOL-1-YL-2-YLIDENE)]BIS(N-HYDROXYMETHANAMINE)'>4VV</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=5bwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bwb OCA], [https://pdbe.org/5bwb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bwb RCSB], [https://www.ebi.ac.uk/pdbsum/5bwb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bwb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ACES_TETCF ACES_TETCF] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions.
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== Publication Abstract from PubMed ==
As part of ongoing efforts to design improved nerve agent antidotes, two X-ray crystal structures of Torpedo californica acetylcholinesterase (TcAChE) bound to the bis-pyridinium oxime, Ortho-7, or its experimental bis-imidazolium analogue, 2BIM-7, were determined. Bis-oximes contain two oxime groups connected by a hydrophobic linker. One oxime group of Ortho-7 binds at the entrance to the active-site gorge near Trp279, and the second binds at the bottom near Trp84 and Phe330. In the Ortho-7-TcAChE complex the oxime at the bottom of the gorge was directed towards the nucleophilic Ser200. In contrast, the oxime group of 2BIM-7 was rotated away from Ser200 and the oxime at the entrance induced a significant conformational change in the peripheral anionic site (PAS) residue Trp279. The conformational change alters the surface of the PAS and positions the imidazolium oxime of 2BIM-7 further from Ser200. The relatively weaker binding and poorer reactivation of VX-inhibited, tabun-inhibited or sarin-inhibited human acetylcholinesterase by 2BIM-7 compared with Ortho-7 may in part be owing to the unproductively bound states caught in crystallo. Overall, the reactivation efficiency of 2BIM-7 was comparable to that of 2-pyridine aldoxime methyl chloride (2-PAM), but unlike 2-PAM the bis-imidazolium oxime lacks a fixed charge, which may affect its membrane permeability.

A conformational change in the peripheral anionic site of Torpedo californica acetylcholinesterase induced by a bis-imidazolium oxime.,Legler PM, Soojhawon I, Millard CB Acta Crystallogr D Biol Crystallogr. 2015 Sep 1;71(Pt 9):1788-98. doi:, 10.1107/S1399004715011281. Epub 2015 Aug 25. PMID:26327369<ref>PMID:26327369</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5bwb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Tetronarce californica]]
[[Category: Legler PM]]
[[Category: Millard CB]]