7r0a
From Proteopedia
(Difference between revisions)
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==Structure of sarin phosphonylated acetylcholinesterase in complex with 2-((hydroxyimino)methyl)-1-(5-(4-methyl-3-nitrobenzamido)pentyl)pyridinium== | ==Structure of sarin phosphonylated acetylcholinesterase in complex with 2-((hydroxyimino)methyl)-1-(5-(4-methyl-3-nitrobenzamido)pentyl)pyridinium== | ||
| - | <StructureSection load='7r0a' size='340' side='right'caption='[[7r0a]]' scene=''> | + | <StructureSection load='7r0a' size='340' side='right'caption='[[7r0a]], [[Resolution|resolution]] 2.80Å' 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=7R0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R0A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7r0a]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R0A 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=7r0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r0a OCA], [https://pdbe.org/7r0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r0a RCSB], [https://www.ebi.ac.uk/pdbsum/7r0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r0a 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=I4H:~{N}-ethyl-4-methyl-3-nitro-benzamide'>I4H</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P15:2,5,8,11,14,17-HEXAOXANONADECAN-19-OL'>P15</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene>, <scene name='pdbligand=TOE:2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXYL'>TOE</scene></td></tr> |
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SGB:O-[(S)-METHYL(1-METHYLETHOXY)PHOSPHORYL]-L-SERINE'>SGB</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]], [[7r2f|7r2f]], [[7r3c|7r3c]], [[7r02|7r02]], [[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=7r0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r0a OCA], [https://pdbe.org/7r0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r0a RCSB], [https://www.ebi.ac.uk/pdbsum/7r0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r0a 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 7r0a" 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: Sarin phosphonylated]] | ||
Revision as of 05:20, 15 June 2022
Structure of sarin phosphonylated acetylcholinesterase in complex with 2-((hydroxyimino)methyl)-1-(5-(4-methyl-3-nitrobenzamido)pentyl)pyridinium
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