View source for 6ezg


==Torpedo californica AChE in complex with indolic multi-target directed ligand==
<StructureSection load='6ezg' size='340' side='right' caption='[[6ezg]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ezg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Tetronarce_californica Tetronarce californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EZG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EZG FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C6K:1-(7-chloranyl-4-methoxy-1~{H}-indol-5-yl)-3-[1-(phenylmethyl)piperidin-4-yl]propan-1-one'>C6K</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ea5|1ea5]], [[2w75|2w75]], [[1eve|1eve]]</td></tr>
<tr id='activity'><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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ezg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ezg OCA], [http://pdbe.org/6ezg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ezg RCSB], [http://www.ebi.ac.uk/pdbsum/6ezg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ezg ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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 ==
Pleiotropic intervention may be a requirement for effective limitation of the progression of multifactorial diseases such as Alzheimer's Disease. One approach to such intervention is to design a single chemical entity capable of acting on two or more targets of interest, which are accordingly known as Multi-Target Directed Ligands (MTDLs). We recently described donecopride, the first MTDL able to simultaneously inhibit acetylcholinesterase and act as an agonist of the 5-HT4 receptor, which displays promising activities in vivo. Pharmacomodulation of donecopride allowed us to develop a novel series of indole derivatives possessing interesting in vitro activities toward AChE and the sigma1 receptor. The crystal structures of complexes of the most promising compounds with Torpedo californica AChE were solved in order to further understand their mode of inhibition.

Novel multitarget-directed ligands targeting acetylcholinesterase and sigma1 receptors as lead compounds for treatment of Alzheimer's disease: Synthesis, evaluation, and structural characterization of their complexes with acetylcholinesterase.,Lalut J, Santoni G, Karila D, Lecoutey C, Davis A, Nachon F, Silman I, Sussman J, Weik M, Maurice T, Dallemagne P, Rochais C Eur J Med Chem. 2018 Nov 8;162:234-248. doi: 10.1016/j.ejmech.2018.10.064. PMID:30447434<ref>PMID:30447434</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ezg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Acetylcholinesterase]]
[[Category: Tetronarce californica]]
[[Category: Dallemagne, P]]
[[Category: Davis, A]]
[[Category: Karila, D]]
[[Category: Lalut, J]]
[[Category: Lecoutey, C]]
[[Category: Maurice, T]]
[[Category: Nachon, F]]
[[Category: Rochais, C]]
[[Category: Santoni, G]]
[[Category: Sillman, I]]
[[Category: Sussman, J]]
[[Category: Weik, M]]
[[Category: Alzheimer desease]]
[[Category: Hydrolase]]
[[Category: Multi-target inhibitor]]