View source for 5ehq


==mAChE-anti TZ2PA5 complex==
<StructureSection load='5ehq' size='340' side='right'caption='[[5ehq]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ehq]] 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=5EHQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EHQ 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]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5O2:6-PHENYL-5-[5-[1-[2-(1,2,3,4-TETRAHYDROACRIDIN-9-YLAMINO)ETHYL]-1,2,3-TRIAZOL-4-YL]PENTYL]PHENANTHRIDIN-5-IUM-3,8-DIAMINE'>5O2</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</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=5ehq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ehq OCA], [https://pdbe.org/5ehq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ehq RCSB], [https://www.ebi.ac.uk/pdbsum/5ehq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ehq 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.
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== Publication Abstract from PubMed ==
Ligand binding sites on acetylcholinesterase (AChE) comprise an active center, at the base of a deep and narrow gorge lined by aromatic residues, and a peripheral site at the gorge entry. These features launched AChE as a reaction vessel for in situ click-chemistry synthesis of high-affinity TZ2PA6 and TZ2PA5 inhibitors, forming a syn-triazole upon cycloaddition within the gorge from alkyne and azide reactants bound at the two sites, respectively. Subsequent crystallographic analyses of AChE complexes with the TZ2PA6 regioisomers demonstrated that syn product association is accompanied by side chain reorganization within the gorge, freezing-in-frame a conformation distinct from an unbound state or anti complex. To correlate inhibitor dimensions with reactivity and explore whether in situ cycloaddition could be accelerated in a concentrated, crystalline template, we developed crystal-soaking procedures and solved structures of AChE complexes with the TZ2PA5 regioisomers and their TZ2/PA5 precursors (2.1-2.7 A resolution). The structures evidence motions of residue His447 in the active site and, unprecedentedly, residue Tyr341 at the gorge mouth, associated with TZ2 binding and coordinated with other side chain motions in the gorge that guide AChE toward a transient state favoring syn-triazole formation. Despite precursor binding to crystalline AChE, coupling of rapid electric field fluctuations in the gorge with proper alignments of the azide and alkyne reactants to form the triazole remains a likely limiting step. These observations point to a prime requirement for AChE to interconvert dynamically between sequential conformations to promote favorable electrostatic factors enabling a productive apposition of the reactants for reactivity.

Steric and dynamic parameters influencing in situ cycloadditions to form triazole inhibitors with crystalline acetylcholinesterase.,Bourne Y, Sharpless KB, Taylor P, Marchot P J Am Chem Soc. 2016 Jan 5. PMID:26731630<ref>PMID:26731630</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 5ehq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Bourne Y]]
[[Category: Marchot P]]