6wuz: Difference between revisions
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==Crystal Structure of Recombinant Human Acetylcholinesterase Inhibited by GB== | ==Crystal Structure of Recombinant Human Acetylcholinesterase Inhibited by GB== | ||
<StructureSection load='6wuz' size='340' side='right'caption='[[6wuz]]' scene=''> | <StructureSection load='6wuz' size='340' side='right'caption='[[6wuz]], [[Resolution|resolution]] 2.25Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WUZ FirstGlance]. <br> | <table><tr><td colspan='2'>[[6wuz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WUZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WUZ FirstGlance]. <br> | ||
</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=6wuz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wuz OCA], [https://pdbe.org/6wuz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wuz RCSB], [https://www.ebi.ac.uk/pdbsum/6wuz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wuz ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.253Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7PE:2-(2-(2-(2-(2-(2-ETHOXYETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHOXY)ETHANOL'>7PE</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UCJ:propan-2-yl+hydrogen+(S)-methylphosphonate'>UCJ</scene></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=6wuz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wuz OCA], [https://pdbe.org/6wuz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wuz RCSB], [https://www.ebi.ac.uk/pdbsum/6wuz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wuz ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://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 == | |||
The recent use of organophosphate nerve agents in Syria, Malaysia, Russia, and the United Kingdom has reinforced the potential threat of their intentional release. These agents act through their ability to inhibit human acetylcholinesterase (hAChE; E.C. 3.1.1.7), an enzyme vital for survival. The toxicity of hAChE inhibition via G-series nerve agents has been demonstrated to vary widely depending on the G-agent used. To gain insight into this issue, the structures of hAChE inhibited by tabun, sarin, cyclosarin, soman, and GP were obtained along with the inhibition kinetics for these agents. Through this information, the role of hAChE active site plasticity in agent selectivity is revealed. With reports indicating that the efficacy of reactivators can vary based on the nerve agent inhibiting hAChE, human recombinatorially expressed hAChE was utilized to define these variations for HI-6 among various G-agents. To identify the structural underpinnings of this phenomenon, the structures of tabun, sarin, and soman-inhibited hAChE in complex with HI-6 were determined. This revealed how the presence of G-agent adducts impacts reactivator access and placement within the active site. These insights will contribute toward a path of next-generation reactivators and an improved understanding of the innate issues with the current reactivators. | |||
Structural and Biochemical Insights into the Inhibition of Human Acetylcholinesterase by G-Series Nerve Agents and Subsequent Reactivation by HI-6.,McGuire JR, Bester SM, Guelta MA, Cheung J, Langley C, Winemiller MD, Bae SY, Funk V, Myslinski JM, Pegan SD, Height JJ Chem Res Toxicol. 2021 Feb 4. doi: 10.1021/acs.chemrestox.0c00406. PMID:33538594<ref>PMID:33538594</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6wuz" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bester SM]] | [[Category: Bester SM]] | ||
Latest revision as of 14:37, 18 October 2023
Crystal Structure of Recombinant Human Acetylcholinesterase Inhibited by GB
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