View source for 2xui


==CRYSTAL STRUCTURE OF MACHE-Y337A-TZ2PA6 SYN COMPLEX (1 WK)==
<StructureSection load='2xui' size='340' side='right'caption='[[2xui]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2xui]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XUI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XUI FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=TZ5:3,8-DIAMINO-6-PHENYL-5-[6-[1-[2-[(1,2,3,4-TETRAHYDRO-9-ACRIDINYL)AMINO]ETHYL]-1H-1,2,3-TRIAZOL-5-YL]HEXYL]-PHENANTHRIDINIUM'>TZ5</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2jgh|2jgh]], [[2whq|2whq]], [[1mah|1mah]], [[2ha6|2ha6]], [[1maa|1maa]], [[2c0q|2c0q]], [[2jgg|2jgg]], [[2jgl|2jgl]], [[2xug|2xug]], [[1q84|1q84]], [[2xud|2xud]], [[2jgm|2jgm]], [[2jge|2jge]], [[1q83|1q83]], [[2wls|2wls]], [[2xup|2xup]], [[1c2b|1c2b]], [[2ha3|2ha3]], [[2ha0|2ha0]], [[2wu3|2wu3]], [[2xuf|2xuf]], [[2jey|2jey]], [[2jgi|2jgi]], [[1n5r|1n5r]], [[2jgj|2jgj]], [[1j06|1j06]], [[2c0p|2c0p]], [[2jf0|2jf0]], [[2xuo|2xuo]], [[2h9y|2h9y]], [[2whr|2whr]], [[1n5m|1n5m]], [[2ha5|2ha5]], [[2ha2|2ha2]], [[2xuq|2xuq]], [[2whp|2whp]], [[2jez|2jez]], [[2jgk|2jgk]], [[1ku6|1ku6]], [[2ha4|2ha4]], [[1j07|1j07]], [[2jgf|2jgf]], [[2ha7|2ha7]], [[2wu4|2wu4]], [[1c2o|1c2o]], [[2xuk|2xuk]], [[2xuj|2xuj]], [[2xuh|2xuh]]</div></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2xui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xui OCA], [https://pdbe.org/2xui PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xui RCSB], [https://www.ebi.ac.uk/pdbsum/2xui PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xui 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. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The active center of acetylcholinesterase (AChE), a target site for competitive inhibitors, resides centrosymmetric to the subunit at the base of a deep, narrow gorge lined by aromatic residues. At the gorge entry, a peripheral site encompasses overlapping binding loci for noncompetitive inhibitors, which alter substrate access to the gorge. The click-chemistry inhibitor TZ2PA6 links the active center ligand, tacrine, to the peripheral site ligand, propidium, through a biorthogonal reaction of an acetylene and an azide that forms either a syn1 or an anti1 triazole. Compared with wild-type mouse AChE, a Tyr337Ala mutant displays full catalytic activity, albeit with 2-3 orders of magnitude higher affinities for the TZ2PA6 syn1 and anti1 regioisomers, reflected in low femtomolar K(d) values, diffusion-limited association, and dissociation half-times greater than 1 month and 1 week, respectively. Three structures of each of the co-crystallized syn1 and anti1 complexes of the Tyr337Ala mutant were solved at three distinct times of crystal maturation, consistent with or exceeding the half-lives of the complexes in solution, while crystalline complexes obtained from soaked Tyr337Ala crystals led to picturing "freshly formed" complexes. The structures, at 2.55-2.75A resolution, reveal a range of unprecedented conformations of the bound regioisomers, not observed in the wild-type AChE complexes, associated with concerted positional rearrangements of side chains in the enzyme gorge. Moreover, time-dependent conformational remodeling of the crystalline complexes appears to correlate with the dissociation half-times of the solution complexes. Hence, for the tight-binding TZ2PA6 inhibitors, the initial complexes kinetically driven in solution slowly form more stable complexes governed by thermodynamic equilibrium and observable in mature crystals.

Conformational Remodeling of Femtomolar Inhibitor-Acetylcholinesterase Complexes in the Crystalline State.,Bourne Y, Radic Z, Taylor P, Marchot P J Am Chem Soc. 2010 Nov 19. PMID:21090615<ref>PMID:21090615</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2xui" style="background-color:#fffaf0;"></div>

==See Also==
*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Acetylcholinesterase]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Bourne, Y]]
[[Category: Marchot, P]]
[[Category: Radic, Z]]
[[Category: Taylor, P]]
[[Category: Click chemistry]]
[[Category: Hydrolase]]
[[Category: Hydrolase fold]]