View source for 6fqn


==Carbamylated T. californica acetylcholineterase bound to uncharged hybrid reactivator 2==
<StructureSection load='6fqn' size='340' side='right'caption='[[6fqn]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fqn]] 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=6FQN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FQN 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]] 2.3000267&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BXT:(2~{S})-2-azanyl-3-[ethyl(methyl)carbamoyl]oxy-propanoic+acid'>BXT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=E2W:6-[4-[(7-chloranyl-1,2,3,4-tetrahydroacridin-9-yl)amino]butyl]-2-[(oxidanylamino)methyl]pyridin-3-ol'>E2W</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</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=6fqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fqn OCA], [https://pdbe.org/6fqn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fqn RCSB], [https://www.ebi.ac.uk/pdbsum/6fqn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fqn 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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Acetylcholinesterase (AChE), a key enzyme in the central and peripheral nervous systems, is the principal target of organophosphorus nerve agents. Quaternary oximes can regenerate AChE activity by displacing the phosphyl group of the nerve agent from the active-site, but they poorly distribute in the central nervous system. A promising reactivator based on tetrahydroacridine linked to a non-quaternary oxime is also an undesired sub-micromolar reversible inhibitor of AChE. X-ray structures and molecular docking indicate that structural modification of tetrahydroacridine might decrease inhibition without affecting reactivation. The chlorinated derivative was synthesized, and, in line with the prediction, displayed a 10-fold decrease in inhibition, but no significant decrease in reactivation efficiency. X-ray structures with the derivative rationalize this outcome. We thus show that rational design based on structural studies permits the refinement of a new generation pyridine aldoxime reactivators that may be more effective in the treatment of nerve agent intoxication.

Structure-based optimization of non-quaternary reactivators of acetylcholinesterase inhibited by organophosphorus nerve agents.,Santoni G, de Sousa J, De la Mora E, Dias J, Jean L, Sussman JL, Silman I, Renard PY, Brown RCD, Weik M, Baati R, Nachon F J Med Chem. 2018 Aug 20. doi: 10.1021/acs.jmedchem.8b00592. PMID:30125110<ref>PMID:30125110</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fqn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Tetronarce californica]]
[[Category: Baati R]]
[[Category: De la Mora E]]
[[Category: Nachon F]]
[[Category: Santoni G]]
[[Category: Silman I]]
[[Category: Sussman J]]
[[Category: Weik M]]
[[Category: De Souza J]]