7d9o - Revision history

OCA at 16:29, 29 November 2023

OCA — Wed, 29 Nov 2023 16:29:08 GMT

←Older revision		Revision as of 16:29, 29 November 2023
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	==Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with Compound 2==		==Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with Compound 2==
-	<StructureSection load='7d9o' size='340' side='right'caption='[[7d9o]]' scene=''>	+	<StructureSection load='7d9o' size='340' side='right'caption='[[7d9o]], [[Resolution\|resolution]] 2.45Å' 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=7D9O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D9O FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7d9o]] is a 2 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=7D9O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D9O 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=7d9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d9o OCA], [https://pdbe.org/7d9o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d9o RCSB], [https://www.ebi.ac.uk/pdbsum/7d9o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d9o 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]] 2.45Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=H0L:(2R)-2-[[4-fluoranyl-1-[(4-fluorophenyl)methyl]piperidin-4-yl]methyl]-5,6-dimethoxy-2,3-dihydroinden-1-one'>H0L</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7d9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d9o OCA], [https://pdbe.org/7d9o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d9o RCSB], [https://www.ebi.ac.uk/pdbsum/7d9o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d9o 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 ==
		+	The acetylcholinesterase (AChE) inhibitors remain key therapeutic drugs for the treatment of Alzheimer's disease (AD). However, the low-safety window limits their maximum therapeutic benefits. Here, a novel kinetics-driven drug design strategy was employed to discover new-generation AChE inhibitors that possess a longer drug-target residence time and exhibit a larger safety window. After detailed investigations, compound 12 was identified as a highly potent, highly selective, orally bioavailable, and brain preferentially distributed AChE inhibitor. Moreover, it significantly ameliorated cognitive impairments in different mouse models with a lower effective dose than donepezil. The X-ray structure of the cocrystal complex provided a precise binding mode between 12 and AChE. Besides, the data from the phase I trials demonstrated that 12 had good safety, tolerance, and pharmacokinetic profiles at all preset doses in healthy volunteers, providing a solid basis for its further investigation in phase II trials for the treatment of AD.
		+
		+	Kinetics-Driven Drug Design Strategy for Next-Generation Acetylcholinesterase Inhibitors to Clinical Candidate.,Zhou Y, Fu Y, Yin W, Li J, Wang W, Bai F, Xu S, Gong Q, Peng T, Hong Y, Zhang D, Zhang D, Liu Q, Xu Y, Xu HE, Zhang H, Jiang H, Liu H J Med Chem. 2021 Feb 25;64(4):1844-1855. doi: 10.1021/acs.jmedchem.0c01863. Epub , 2021 Feb 11. PMID:33570950<ref>PMID:33570950</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7d9o" 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: Liu QF]]		[[Category: Liu QF]]
	[[Category: Yin WC]]		[[Category: Yin WC]]

OCA at 06:18, 25 August 2021

OCA — Wed, 25 Aug 2021 06:18:06 GMT

←Older revision		Revision as of 06:18, 25 August 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7d9o ~~is ON HOLD until Paper Publication~~	+	==Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with Compound 2==
-		+	<StructureSection load='7d9o' size='340' side='right'caption='[[7d9o]]' scene=''>
-	~~Authors~~: ~~Liu~~, Q.F., ~~Yin~~, W.C.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7D9O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D9O FirstGlance]. <br>
-	~~Description: Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with Compound 2~~	+	</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=7d9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d9o OCA], [https://pdbe.org/7d9o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d9o RCSB], [https://www.ebi.ac.uk/pdbsum/7d9o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d9o ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Yin, W.C~~]]	+	__TOC__
-	[[Category: ~~Liu, Q.F~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Liu QF]]
		+	[[Category: Yin WC]]

OCA at 05:20, 25 November 2020

OCA — Wed, 25 Nov 2020 05:20:28 GMT

←Older revision		Revision as of 05:20, 25 November 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7d9o is ON HOLD	+	The entry 7d9o is ON HOLD until Paper Publication

	Authors: Liu, Q.F., Yin, W.C.		Authors: Liu, Q.F., Yin, W.C.

OCA: Protected "7d9o" [edit=sysop:move=sysop]

OCA — Wed, 21 Oct 2020 06:46:09 GMT

Protected "7d9o" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:46, 21 October 2020

OCA: New page: '''Unreleased structure''' The entry 7d9o is ON HOLD Authors: Liu, Q.F., Yin, W.C. Description: Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with Compound 2 [...

OCA — Wed, 21 Oct 2020 06:46:08 GMT

New page: '''Unreleased structure''' The entry 7d9o is ON HOLD Authors: Liu, Q.F., Yin, W.C. Description: Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with Compound 2 [...

New page

'''Unreleased structure'''

The entry 7d9o is ON HOLD

Authors: Liu, Q.F., Yin, W.C.

Description: Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with Compound 2
[[Category: Unreleased Structures]]
[[Category: Yin, W.C]]
[[Category: Liu, Q.F]]