6cqz: Difference between revisions
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==Crystal Structure of Recombinant Human Acetylcholinesterase Inhibited by VX== | ==Crystal Structure of Recombinant Human Acetylcholinesterase Inhibited by VX== | ||
<StructureSection load='6cqz' size='340' side='right' caption='[[6cqz]], [[Resolution|resolution]] 2.22Å' scene=''> | <StructureSection load='6cqz' size='340' side='right'caption='[[6cqz]], [[Resolution|resolution]] 2.22Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6cqz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CQZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CQZ FirstGlance]. <br> | <table><tr><td colspan='2'>[[6cqz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CQZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CQZ FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=VX:O-ETHYLMETHYLPHOSPHONIC+ACID+ESTER+GROUP'>VX</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=VX:O-ETHYLMETHYLPHOSPHONIC+ACID+ESTER+GROUP'>VX</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6cqw|6cqw]], [[6cqx|6cqx]], [[6cqy|6cqy]], [[6cqt|6cqt]], [[6cqu|6cqu]], [[6cqv|6cqv]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6cqw|6cqw]], [[6cqx|6cqx]], [[6cqy|6cqy]], [[6cqt|6cqt]], [[6cqu|6cqu]], [[6cqv|6cqv]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACHE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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=6cqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cqz OCA], [http://pdbe.org/6cqz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cqz RCSB], [http://www.ebi.ac.uk/pdbsum/6cqz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cqz ProSAT]</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=6cqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cqz OCA], [http://pdbe.org/6cqz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cqz RCSB], [http://www.ebi.ac.uk/pdbsum/6cqz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cqz ProSAT]</span></td></tr> | ||
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</div> | </div> | ||
<div class="pdbe-citations 6cqz" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6cqz" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Acetylcholinesterase]] | [[Category: Acetylcholinesterase]] | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Bester, S M]] | [[Category: Bester, S M]] | ||
[[Category: Guelta, M A]] | [[Category: Guelta, M A]] | ||
Revision as of 09:59, 27 March 2019
Crystal Structure of Recombinant Human Acetylcholinesterase Inhibited by VXCrystal Structure of Recombinant Human Acetylcholinesterase Inhibited by VX
Structural highlights
Function[ACES_HUMAN] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.[1] [2] [3] [4] Publication Abstract from PubMedOver 50 years ago, the toxicity of irreversible organophosphate inhibitors targeting human acetylcholinesterase (hAChE) were observed to be stereospecific. The therapeutic reversal of hAChE inhibition by reactivators has also been shown to depend on the stereochemistry of the inhibitor. To gain clarity on the mechanism of stereospecific inhibition, the X-ray crystallographic structures hAChE inhibited by a racemic mixture of VX (PR/S) and its enantiomers were obtained. Beyond identifying hAChE structural features that lend themselves to stereospecific inhibition, structures of the reactivator HI-6 bound to hAChEs inhibited by VX enantiomers of varying toxicity, or in its uninhibited state, were obtained. Comparison of hAChE in these pre-reactivation and post-reactivation states along with enzymatic data reveals the potential influence of unproductive reactivator poses on the efficacy of these types of therapeutics. The recognition of structural features related to hAChE's stereospecificity towards VX shed light on the molecular influences of toxicity and their effect on reactivators. In addition to providing a better understanding of the innate issues with current reactivators, an avenue for improvement of reactivators is envisioned. Structural insights of stereospecific inhibition of human acetylcholinesterase by VX and subsequent reactivation by HI-6.,Bester SM, Guelta MA, Cheung J, Winemiller MD, Bae SY, Myslinski J, Pegan SD, Height JJ Chem Res Toxicol. 2018 Nov 21. doi: 10.1021/acs.chemrestox.8b00294. PMID:30462502[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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