View source for 4bdt


==Human acetylcholinesterase in complex with huprine W and fasciculin 2==
<StructureSection load='4bdt' size='340' side='right'caption='[[4bdt]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4bdt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Dendroaspis_angusticeps Dendroaspis angusticeps] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BDT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BDT 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]] 3.104&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=HUW:HUPRINE+W'>HUW</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4bdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bdt OCA], [https://pdbe.org/4bdt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bdt RCSB], [https://www.ebi.ac.uk/pdbsum/4bdt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bdt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ACES_HUMAN ACES_HUMAN] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.<ref>PMID:2714437</ref> <ref>PMID:1748670</ref> <ref>PMID:1517212</ref> <ref>PMID:11985878</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The multifunctional nature of Alzheimer's disease calls for multi-target directed ligands (MTDLs) able to act on different components of the pathology, like the cholinergic dysfunction and amyloid aggregation. Such MTDLs are usually based on cholinesterase inhibitors (e.g., tacrine or huprine) coupled to another active molecule aimed at a different target. To aid in the design of these MTDLs we report the crystal structures of human acetylcholinesterase (hAChE) in complex with FAS-2 and a hydroxylated derivative of huprine (huprine W), and of human butyrylcholinesterase (hBChE) in complex with tacrine. Huprine W in hAChE and tacrine in hBChE reside in strikingly similar positions highlighting the conservation of key interactions, namely, pi-pi/cation-pi interactions with Trp86(82), and hydrogen bonding with the main chain carbonyl of the catalytic histidine. Huprine W forms additional interactions with hAChE which explains its superior affinity: the isoquinoline moiety is associated with a group of aromatic residues (Tyr337, Phe338 and Phe295 not present in hBChE) in addition to Trp86; the hydroxyl group is hydrogen bonded to both the catalytic serine and residues in the oxyanion hole; and the chlorine substituent is nested in a hydrophobic pocket interacting strongly with Trp439. There is no pocket in hBChE able to accommodate the chlorine substituent.

Crystal Structures of Human Cholinesterases in Complex with Huprine W and Tacrine: Elements of Specificity for Anti-Alzheimer's Drugs Targeting Acetyl- and Butyrylcholinesterase.,Nachon F, Carletti E, Ronco C, Trovaslet M, Nicolet Y, Jean L, Renard PY Biochem J. 2013 May 17. PMID:23679855<ref>PMID:23679855</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4bdt" style="background-color:#fffaf0;"></div>

==See Also==
*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]]
*[[Fasciculin|Fasciculin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dendroaspis angusticeps]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Carletti E]]
[[Category: Jean L]]
[[Category: Nachon F]]
[[Category: Nicolet Y]]
[[Category: Renard P-Y]]
[[Category: Ronco C]]
[[Category: Trovaslet M]]