6g1v: Difference between revisions
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==Crystal structure of Torpedo Californica acetylcholinesterase in complex with 12-Amino-3-chloro-6,7,10,11-tetrahydro-5,9-dimethyl-7,11-methanocycloocta[b]quinolin-5-ium== | |||
<StructureSection load='6g1v' size='340' side='right' caption='[[6g1v]], [[Resolution|resolution]] 1.82Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6g1v]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Tetronarce_californica Tetronarce californica]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6fou 6fou]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G1V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G1V FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=E1N:12-Amino-3-chloro-6,7,10,11-tetrahydro-5,9-dimethyl-7,11-methanocycloocta[b]quinolin-5-ium'>E1N</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></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=6g1v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g1v OCA], [http://pdbe.org/6g1v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g1v RCSB], [http://www.ebi.ac.uk/pdbsum/6g1v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g1v 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 == | |||
Symptomatic treatment of myasthenia gravis is based on the use of peripherally-acting acetylcholinesterase (AChE) inhibitors that, in some cases, must be discontinued due to the occurrence of a number of side-effects. Thus, new AChE inhibitors are being developed and investigated for their potential use against this disease. Here, we have explored two alternative approaches to get access to peripherally-acting AChE inhibitors as new agents against myasthenia gravis, by structural modification of the brain permeable anti-Alzheimer AChE inhibitors tacrine, 6-chlorotacrine, and huprine Y. Both quaternization upon methylation of the quinoline nitrogen atom, and tethering of a triazole ring, with, in some cases, the additional incorporation of a polyphenol-like moiety, result in more polar compounds with higher inhibitory activity against human AChE (up to 190-fold) and butyrylcholinesterase (up to 40-fold) than pyridostigmine, the standard drug for symptomatic treatment of myasthenia gravis. The novel compounds are furthermore devoid of brain permeability, thereby emerging as interesting leads against myasthenia gravis. | |||
Increasing Polarity in Tacrine and Huprine Derivatives: Potent Anticholinesterase Agents for the Treatment of Myasthenia Gravis.,Galdeano C, Coquelle N, Cieslikiewicz-Bouet M, Bartolini M, Perez B, Clos MV, Silman I, Jean L, Colletier JP, Renard PY, Munoz-Torrero D Molecules. 2018 Mar 11;23(3). pii: molecules23030634. doi:, 10.3390/molecules23030634. PMID:29534488<ref>PMID:29534488</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6g1v" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Acetylcholinesterase]] | |||
[[Category: Tetronarce californica]] | |||
[[Category: Colletier, J P]] | |||
[[Category: Coquelle, N]] | [[Category: Coquelle, N]] | ||
[[Category: | [[Category: Ad]] | ||
[[Category: Alzheimer disease]] | |||
[[Category: Hydrolase]] | |||
[[Category: Torpedo californica acetylcholinesterase]] | |||
