7p1n
From Proteopedia
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| - | ==== | + | ==Crystal structure of human acetylcholinesterase in complex with (2R,3R,4S,5S,6R)-2-{4-[1-(4-{5-hydroxy-6-[(E)-(hydroxyimino)methyl]pyridin-2-yl}butyl)-1H-1,2,3-triazol-4-yl]butoxy}-6-(hydroxymethyl)oxane-3,4,5-triol oxime== |
| - | <StructureSection load='7p1n' size='340' side='right'caption='[[7p1n]]' scene=''> | + | <StructureSection load='7p1n' size='340' side='right'caption='[[7p1n]], [[Resolution|resolution]] 2.95Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7p1n]] is a 4 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=7P1N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P1N 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=7p1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p1n OCA], [https://pdbe.org/7p1n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p1n RCSB], [https://www.ebi.ac.uk/pdbsum/7p1n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p1n 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]] 2.95Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4J1:(2~{R},3~{R},4~{S},5~{S},6~{R})-2-[4-[1-[4-[6-[(~{Z})-hydroxyiminomethyl]-5-oxidanyl-pyridin-2-yl]butyl]-1,2,3-triazol-4-yl]butoxy]-6-(hydroxymethyl)oxane-3,4,5-triol'>4J1</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7p1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p1n OCA], [https://pdbe.org/7p1n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p1n RCSB], [https://www.ebi.ac.uk/pdbsum/7p1n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p1n ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Recent events demonstrated that organophosphorus nerve agents are a serious threat for civilian and military populations. The current therapy includes a pyridinium aldoxime reactivator to restore the enzymatic activity of acetylcholinesterase located in the central nervous system and neuro-muscular junctions. One major drawback of these charged acetylcholinesterase reactivators is their poor ability to cross the blood-brain barrier. In this study, we propose to evaluate glucoconjugated oximes devoid of permanent charge as potential central nervous system reactivators. We determined their in vitro reactivation efficacy on inhibited human acetylcholinesterase, the crystal structure of two compounds in complex with the enzyme, their protective index on intoxicated mice, and their pharmacokinetics. We then evaluated their endothelial permeability coefficients with a human in vitro model. This study shed light on the structural restrains of new sugar oximes designed to reach the central nervous system through the glucose transporter located at the blood-brain barrier. | ||
| + | |||
| + | A New Class of Bi- and Trifunctional Sugar Oximes as Antidotes against Organophosphorus Poisoning.,Da Silva O, Probst N, Landry C, Hanak AS, Warnault P, Coisne C, Calas AG, Gosselet F, Courageux C, Gastellier AJ, Trancart M, Baati R, Dehouck MP, Jean L, Nachon F, Renard PY, Dias J J Med Chem. 2022 Mar 24;65(6):4649-4666. doi: 10.1021/acs.jmedchem.1c01748. Epub , 2022 Mar 7. PMID:35255209<ref>PMID:35255209</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7p1n" 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: | + | [[Category: Da Silva O]] |
| + | [[Category: Dias J]] | ||
| + | [[Category: Nachon F]] | ||
Current revision
Crystal structure of human acetylcholinesterase in complex with (2R,3R,4S,5S,6R)-2-{4-[1-(4-{5-hydroxy-6-[(E)-(hydroxyimino)methyl]pyridin-2-yl}butyl)-1H-1,2,3-triazol-4-yl]butoxy}-6-(hydroxymethyl)oxane-3,4,5-triol oxime
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