7r2f
From Proteopedia
(Difference between revisions)
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==Structure of tabun inhibited acetylcholinesterase in complex with 2-((hydroxyimino)methyl)-1-(5-(4-methyl-3-nitrobenzamido)pentyl)pyridinium== | ==Structure of tabun inhibited acetylcholinesterase in complex with 2-((hydroxyimino)methyl)-1-(5-(4-methyl-3-nitrobenzamido)pentyl)pyridinium== | ||
| - | <StructureSection load='7r2f' size='340' side='right'caption='[[7r2f]]' scene=''> | + | <StructureSection load='7r2f' size='340' side='right'caption='[[7r2f]], [[Resolution|resolution]] 2.30Å' 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=7R2F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R2F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7r2f]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R2F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R2F 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=7r2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r2f OCA], [https://pdbe.org/7r2f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r2f RCSB], [https://www.ebi.ac.uk/pdbsum/7r2f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r2f ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7PG:2,5,8,11,14,17,20,23-OCTAOXAPENTACOSAN-25-OL'>7PG</scene>, <scene name='pdbligand=I1X:4-methyl-3-nitro-~{N}-[(2~{E},4~{E})-5-[2-[(oxidanylamino)methyl]pyridin-1-yl]penta-2,4-dienyl]benzamide'>I1X</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene></td></tr> |
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SUN:O-[(R)-(DIMETHYLAMINO)(ETHOXY)PHOSPHORYL]-L-SERINE'>SUN</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7qyn|7qyn]], [[7r0a|7r0a]], [[7r02|7r02]], [[7r3c|7r3c]], [[7r4e|7r4e]]</div></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=7r2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r2f OCA], [https://pdbe.org/7r2f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r2f RCSB], [https://www.ebi.ac.uk/pdbsum/7r2f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r2f ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == 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 == | ||
| + | Reactivators are vital for the treatment of organophosphorus nerve agent (OPNA) intoxication but new alternatives are needed due to their limited clinical applicability. The toxicity of OPNAs stems from covalent inhibition of the essential enzyme acetylcholinesterase (AChE), which reactivators relieve via a chemical reaction with the inactivated enzyme. Here, we present new strategies and tools for developing reactivators. We discover suitable inhibitor scaffolds by using an activity-independent competition assay to study non-covalent interactions with OPNA-AChEs and transform these inhibitors into broad-spectrum reactivators. Moreover, we identify determinants of reactivation efficiency by analysing reactivation and pre-reactivation kinetics together with structural data. Our results show that new OPNA reactivators can be discovered rationally by exploiting detailed knowledge of the reactivation mechanism of OPNA-inhibited AChE. | ||
| + | |||
| + | Broad-spectrum antidote discovery by untangling the reactivation mechanism of nerve agent inhibited acetylcholinesterase.,Lindgren C, Forsgren N, Hoster N, Akfur C, Artursson E, Edvinsson L, Svensson R, Worek F, Ekstrom F, Linusson A Chemistry. 2022 Apr 14. doi: 10.1002/chem.202200678. PMID:35420233<ref>PMID:35420233</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7r2f" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Acetylcholinesterase]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Edvinsson L]] | + | [[Category: Edvinsson, L]] |
| - | [[Category: Ekstrom F]] | + | [[Category: Ekstrom, F]] |
| - | [[Category: Forsgren N]] | + | [[Category: Forsgren, N]] |
| - | [[Category: Lindgren C]] | + | [[Category: Lindgren, C]] |
| - | [[Category: Linusson A]] | + | [[Category: Linusson, A]] |
| + | [[Category: Complex]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Reactivator]] | ||
| + | [[Category: Tabun phosphylated]] | ||
Revision as of 05:20, 15 June 2022
Structure of tabun inhibited acetylcholinesterase in complex with 2-((hydroxyimino)methyl)-1-(5-(4-methyl-3-nitrobenzamido)pentyl)pyridinium
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