7p1n - Revision history

OCA at 12:59, 1 February 2024

2024-02-01T12:59:55Z

←Older revision		Revision as of 12:59, 1 February 2024
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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:(2R,3R,4S,5S,6R)-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>
		+	== 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 ==
		+	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: ~~Z-disk~~]]	+	[[Category: Da Silva O]]
		+	[[Category: Dias J]]
		+	[[Category: Nachon F]]

OCA at 05:28, 8 June 2022

2022-06-08T05:28:47Z

←Older revision		Revision as of 05:28, 8 June 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7p1n ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7p1n' size='340' side='right'caption='[[7p1n]]' scene=''>
-	~~Authors~~: ~~Da Silva, O~~.~~, Dias, J~~.~~, Nachon, F~~.	+	== 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>
-	~~Description~~: ~~Crystal structure of human acetylcholinesterase in complexe 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~~	+	</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>
-	[~~[Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[~~[Category~~: ~~Nachon~~, F]]	+	__TOC__
-	[[Category: ~~Da Silva, O~~]]	+	</StructureSection>
-	[[Category: ~~Dias, J~~]]	+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 11:58, 17 November 2021

2021-11-17T11:58:32Z

←Older revision		Revision as of 11:58, 17 November 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7p1n is ON HOLD	+	The entry 7p1n is ON HOLD until Paper Publication

	Authors: Da Silva, O., Dias, J., Nachon, F.		Authors: Da Silva, O., Dias, J., Nachon, F.

OCA at 04:03, 6 October 2021

2021-10-06T04:03:32Z

←Older revision		Revision as of 04:03, 6 October 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7p1n is ON HOLD ~~until Paper Publication~~	+	The entry 7p1n is ON HOLD

	Authors: Da Silva, O., Dias, J., Nachon, F.		Authors: Da Silva, O., Dias, J., Nachon, F.

OCA at 09:28, 28 July 2021

2021-07-28T09:28:00Z

←Older revision		Revision as of 09:28, 28 July 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7p1n is ON HOLD	+	The entry 7p1n is ON HOLD until Paper Publication

	Authors: Da Silva, O., Dias, J., Nachon, F.		Authors: Da Silva, O., Dias, J., Nachon, F.

OCA: Protected "7p1n" [edit=sysop:move=sysop]

2021-07-07T08:56:21Z

Protected "7p1n" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:56, 7 July 2021

OCA: New page: '''Unreleased structure''' The entry 7p1n is ON HOLD Authors: Da Silva, O., Dias, J., Nachon, F. Description: Crystal structure of human acetylcholinesterase in complexe with (2R,3R,4S...

2021-07-07T08:56:20Z

New page: '''Unreleased structure''' The entry 7p1n is ON HOLD Authors: Da Silva, O., Dias, J., Nachon, F. Description: Crystal structure of human acetylcholinesterase in complexe with (2R,3R,4S...

New page

'''Unreleased structure'''

The entry 7p1n is ON HOLD

Authors: Da Silva, O., Dias, J., Nachon, F.

Description: Crystal structure of human acetylcholinesterase in complexe 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
[[Category: Unreleased Structures]]
[[Category: Nachon, F]]
[[Category: Da Silva, O]]
[[Category: Dias, J]]