6zwe - Revision history

OCA at 11:59, 1 February 2024

OCA — Thu, 01 Feb 2024 11:59:22 GMT

←Older revision		Revision as of 11:59, 1 February 2024
Line 1:		Line 1:

	==Crystal structure of human acetylcholinesterase in complex with ((6-((2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienamido)hexyl)triphenylphosphonium bromide)==		==Crystal structure of human acetylcholinesterase in complex with ((6-((2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienamido)hexyl)triphenylphosphonium bromide)==
-	<StructureSection load='6zwe' size='340' side='right'caption='[[6zwe]]' scene=''>	+	<StructureSection load='6zwe' size='340' side='right'caption='[[6zwe]], [[Resolution\|resolution]] 3.00Å' 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=6ZWE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZWE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6zwe]] 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=6ZWE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZWE 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=6zwe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zwe OCA], [https://pdbe.org/6zwe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zwe RCSB], [https://www.ebi.ac.uk/pdbsum/6zwe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zwe 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]] 3Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=QRH:(2~{E},4~{E})-5-(1,3-benzodioxol-5-yl)-~{N}-[6-(triphenyl-$l^{5}-phosphanyl)hexyl]penta-2,4-dienamide'>QRH</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=6zwe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zwe OCA], [https://pdbe.org/6zwe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zwe RCSB], [https://www.ebi.ac.uk/pdbsum/6zwe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zwe 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 ==
		+	Neurotransmitter depletion and mitochondrial dysfunction are among the multiple pathological events that lead to neurodegeneration. Following our previous studies related with the development of multitarget mitochondriotropic antioxidants, this study aims to evaluate whether the pi-system extension on the chemical scaffolds of AntiOXCIN2 and AntiOXCIN3 affects their bioactivity and safety profiles. After the synthesis of four triphenylphosphonium (TPP(+)) conjugates (compounds 2-5), we evaluated their antioxidant properties and their effect on neurotransmitter-metabolizing enzymes. All compounds were potent equine butyrylcholinesterase (eqBChE) and moderate electric eel acetylcholinesterase (eeAChE) inhibitors, with catechols 4 and 5 presenting lower IC50 values than AntiOXCIN2 and AntiOXCIN3, respectively. However, differences in the inhibition potency and selectivity of compounds 2-5 towards non-human and human cholinesterases (ChEs) were observed. Co-crystallization studies with compounds 2-5 in complex with human ChEs (hChEs) showed that these compounds exhibit different binging modes to hAChE and hBChE. Unlike AntiOXCINs, compounds 2-5 displayed moderate human monoamine oxidase (hMAO) inhibitory activity. Moreover, compounds 4 and 5 presented higher ORAC-FL indexes and lower oxidation potential values than the corresponding AntiOXCINs. Catechols 4 and 5 exhibited broader safety windows in differentiated neuroblastoma cells than benzodioxole derivatives 2 and 3. Compound 4 is highlighted as a safe mitochondria-targeted antioxidant with dual ChE/MAO inhibitory activity. Overall, this work is a contribution for the development of dual therapeutic agents addressing both mitochondrial oxidative stress and neurotransmitter depletion.
		+
		+	Fine-Tuning the Biological Profile of Multitarget Mitochondriotropic Antioxidants for Neurodegenerative Diseases.,Chavarria D, Da Silva O, Benfeito S, Barreiro S, Garrido J, Cagide F, Soares P, Remiao F, Brazzolotto X, Nachon F, Oliveira PJ, Dias J, Borges F Antioxidants (Basel). 2021 Feb 23;10(2). pii: antiox10020329. doi:, 10.3390/antiox10020329. PMID:33672269<ref>PMID:33672269</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6zwe" 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: Brazzolotto X]]		[[Category: Brazzolotto X]]

OCA at 12:11, 9 June 2021

OCA — Wed, 09 Jun 2021 12:11:25 GMT

←Older revision		Revision as of 12:11, 9 June 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 6zwe is ON HOLD until Paper Publication~~	+	==Crystal structure of human acetylcholinesterase in complex with ((6-((2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienamido)hexyl)triphenylphosphonium bromide)==
-		+	<StructureSection load='6zwe' size='340' side='right'caption='[[6zwe]]' scene=''>
-	~~Authors: Da Silva, O., Dias, J., Nachon, F., Brazzolotto, X.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZWE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZWE FirstGlance]. <br>
-	~~Description:~~ Crystal structure of human acetylcholinesterase in complex with ((6-((2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienamido)hexyl)triphenylphosphonium bromide)	+	</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=6zwe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zwe OCA], [https://pdbe.org/6zwe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zwe RCSB], [https://www.ebi.ac.uk/pdbsum/6zwe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zwe ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Brazzolotto~~, X]]	+	__TOC__
-	[[Category: ~~Nachon, F~~]]	+	</StructureSection>
-	[[Category: Da Silva, O]]	+	[[Category: Large Structures]]
-	[[Category: Dias, J]]	+	[[Category: Brazzolotto X]]
		+	[[Category: Da Silva O]]
		+	[[Category: Dias J]]
		+	[[Category: Nachon F]]

OCA at 04:57, 2 September 2020

OCA — Wed, 02 Sep 2020 04:57:24 GMT

←Older revision		Revision as of 04:57, 2 September 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6zwe is ON HOLD	+	The entry 6zwe is ON HOLD until Paper Publication

	Authors: Da Silva, O., Dias, J., Nachon, F., Brazzolotto, X.		Authors: Da Silva, O., Dias, J., Nachon, F., Brazzolotto, X.
Line 7:		Line 7:
	Description: Crystal structure of human acetylcholinesterase in complex with ((6-((2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienamido)hexyl)triphenylphosphonium bromide)		Description: Crystal structure of human acetylcholinesterase in complex with ((6-((2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienamido)hexyl)triphenylphosphonium bromide)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Brazzolotto, X]]
	[[Category: Nachon, F]]		[[Category: Nachon, F]]
	[[Category: Da Silva, O]]		[[Category: Da Silva, O]]
-	[[Category: Brazzolotto, X]]
	[[Category: Dias, J]]		[[Category: Dias, J]]

OCA: Protected "6zwe" [edit=sysop:move=sysop]

OCA — Wed, 05 Aug 2020 04:00:56 GMT

Protected "6zwe" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:00, 5 August 2020

OCA: New page: '''Unreleased structure''' The entry 6zwe is ON HOLD Authors: Da Silva, O., Dias, J., Nachon, F., Brazzolotto, X. Description: Crystal structure of human acetylcholinesterase in comple...

OCA — Wed, 05 Aug 2020 04:00:55 GMT

New page: '''Unreleased structure''' The entry 6zwe is ON HOLD Authors: Da Silva, O., Dias, J., Nachon, F., Brazzolotto, X. Description: Crystal structure of human acetylcholinesterase in comple...

New page

'''Unreleased structure'''

The entry 6zwe is ON HOLD

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

Description: Crystal structure of human acetylcholinesterase in complex with ((6-((2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienamido)hexyl)triphenylphosphonium bromide)
[[Category: Unreleased Structures]]
[[Category: Nachon, F]]
[[Category: Da Silva, O]]
[[Category: Brazzolotto, X]]
[[Category: Dias, J]]