7r4e: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7r4e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R4E FirstGlance]. <br> | <table><tr><td colspan='2'>[[7r4e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7R4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R4E FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=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=RVX:O-[METHYL(2-METHYLPROPOXY)PHOSPHORYL]-L-SERINE'>RVX</scene>, <scene name='pdbligand=TOE:2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXYL'>TOE</scene></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]] 3.0000117Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=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=RVX:O-[METHYL(2-METHYLPROPOXY)PHOSPHORYL]-L-SERINE'>RVX</scene>, <scene name='pdbligand=TOE:2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXYL'>TOE</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=7r4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r4e OCA], [https://pdbe.org/7r4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r4e RCSB], [https://www.ebi.ac.uk/pdbsum/7r4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r4e ProSAT]</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=7r4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r4e OCA], [https://pdbe.org/7r4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r4e RCSB], [https://www.ebi.ac.uk/pdbsum/7r4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r4e ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Latest revision as of 16:26, 1 February 2024
RVX-inhibited acetylcholinesterase in complex with 2-((hydroxyimino)methyl)-1-(5-(4-methyl-3-nitrobenzamido)pentyl)pyridiniumRVX-inhibited acetylcholinesterase in complex with 2-((hydroxyimino)methyl)-1-(5-(4-methyl-3-nitrobenzamido)pentyl)pyridinium
Structural highlights
FunctionACES_MOUSE Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Publication Abstract from PubMedReactivators 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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