5hf9
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human acetylcholinesterase in complex with paraoxon and HI6== | |
| + | <StructureSection load='5hf9' size='340' side='right' caption='[[5hf9]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5hf9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HF9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HF9 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DEP:DIETHYL+PHOSPHONATE'>DEP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=HI6:4-(AMINOCARBONYL)-1-[({2-[(E)-(HYDROXYIMINO)METHYL]PYRIDINIUM-1-YL}METHOXY)METHYL]PYRIDINIUM'>HI6</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=PE8:3,6,9,12,15,18,21-HEPTAOXATRICOSANE-1,23-DIOL'>PE8</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hf5|5hf5]], [[5hf6|5hf6]], [[5hf8|5hf8]], [[5hfa|5hfa]]</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=5hf9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hf9 OCA], [http://pdbe.org/5hf9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hf9 RCSB], [http://www.ebi.ac.uk/pdbsum/5hf9 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/ACES_HUMAN ACES_HUMAN]] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.<ref>PMID:2714437</ref> <ref>PMID:1748670</ref> <ref>PMID:1517212</ref> <ref>PMID:11985878</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Irreversible inhibition of the essential nervous system enzyme acetylcholinesterase by organophosphate nerve agents and pesticides may quickly lead to death. Oxime reactivators currently used as antidotes are generally less effective against pesticide exposure than nerve agent exposure, and pesticide exposure constitutes the majority of cases of organophosphate poisoning in the world. The current lack of published structural data specific to human acetylcholinesterase organophosphate-inhibited and oxime-bound states hinders development of effective medical treatments. We have solved structures of human acetylcholinesterase in different states in complex with the organophosphate insecticide, paraoxon, and oximes. Reaction with paraoxon results in a highly perturbed acyl loop that causes a narrowing of the gorge in the peripheral site that may impede entry of reactivators. This appears characteristic of acetylcholinesterase inhibition by organophosphate insecticides but not nerve agents. Additional changes seen at the dimer interface are novel and provide further examples of the disruptive effect of paraoxon. Ternary structures of paraoxon-inhibited human acetylcholinesterase in complex with the oximes HI6 and 2-PAM reveals relatively poor positioning for reactivation. This study provides a structural foundation for improved reactivator design for the treatment of organophosphate intoxication. This article is protected by copyright. All rights reserved. | ||
| - | + | Structures of paraoxon-inhibited human acetylcholinesterase reveal perturbations of the acyl loop and the dimer interface.,Franklin MC, Rudolph MJ, Ginter C, Cassidy MS, Cheung J Proteins. 2016 May 18. doi: 10.1002/prot.25073. PMID:27191504<ref>PMID:27191504</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5hf9" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Acetylcholinesterase]] | ||
| + | [[Category: Cassidy, M S]] | ||
| + | [[Category: Cheung, J]] | ||
| + | [[Category: Franklin, M F]] | ||
| + | [[Category: Ginter, C]] | ||
| + | [[Category: Rudolph, M J]] | ||
| + | [[Category: Hydrolase]] | ||
Revision as of 23:15, 23 June 2016
Crystal structure of human acetylcholinesterase in complex with paraoxon and HI6
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