5ov9: Difference between revisions
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==Crystal structure of Acetylcholinesterase in complex with Crystal Violet== | ==Crystal structure of Acetylcholinesterase in complex with Crystal Violet== | ||
<StructureSection load='5ov9' size='340' side='right' caption='[[5ov9]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='5ov9' size='340' side='right'caption='[[5ov9]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ov9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OV9 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5ov9]] 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=5OV9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OV9 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AE3:2-(2-ETHOXYETHOXY)ETHANOL'>AE3</scene>, <scene name='pdbligand=CVI:CRYSTAL+VIOLET'>CVI</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ETX:2-ETHOXYETHANOL'>ETX</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AE3:2-(2-ETHOXYETHOXY)ETHANOL'>AE3</scene>, <scene name='pdbligand=CVI:CRYSTAL+VIOLET'>CVI</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ETX:2-ETHOXYETHANOL'>ETX</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ov9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ov9 OCA], [https://pdbe.org/5ov9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ov9 RCSB], [https://www.ebi.ac.uk/pdbsum/5ov9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ov9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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 == | |||
Acetylcholinesterase (AChE) is an essential enzyme that terminates cholinergic transmission by a rapid hydrolysis of the neurotransmitter acetylcholine. AChE is an important target for treatment of various cholinergic deficiencies, including Alzheimer's disease and myasthenia gravis. In a previous high throughput screening campaign, we identified the dye crystal violet (CV) as an inhibitor of AChE. Herein, we show that CV displays a significant cooperativity for binding to AChE, and the molecular basis for this observation has been investigated by X-ray crystallography. Two monomers of CV bind to residues at the entrance of the active site gorge of the enzyme. Notably, the two CV molecules have extensive intermolecular contacts with each other and with AChE. Computational analyses show that the observed CV dimer is not stable in solution, suggesting the sequential binding of two monomers. Guided by the structural analysis, we designed a set of single site substitutions, and investigated their effect on the binding of CV. Only moderate effects on the binding and the cooperativity were observed, suggesting a robustness in the interaction between CV and AChE. Taken together, we propose that the dimeric cooperative binding is due to a rare combination of chemical and structural properties of both CV and the AChE molecule itself. | |||
An Unusual Dimeric Inhibitor of Acetylcholinesterase: Cooperative Binding of Crystal Violet.,Allgardsson A, David Andersson C, Akfur C, Worek F, Linusson A, Ekstrom F Molecules. 2017 Aug 30;22(9). pii: E1433. doi: 10.3390/molecules22091433. PMID:28867801<ref>PMID:28867801</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5ov9" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Akfur | [[Category: Mus musculus]] | ||
[[Category: Allgardsson | [[Category: Akfur C]] | ||
[[Category: Andersson | [[Category: Allgardsson A]] | ||
[[Category: Ekstrom | [[Category: Andersson CD]] | ||
[[Category: Linusson | [[Category: Ekstrom F]] | ||
[[Category: Worek | [[Category: Linusson A]] | ||
[[Category: Worek F]] | |||