7bgc - Revision history

OCA at 12:28, 1 February 2024

2024-02-01T12:28:02Z

← Older revision		Revision as of 12:28, 1 February 2024
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	<StructureSection load='7bgc' size='340' side='right'caption='[[7bgc]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='7bgc' size='340' side='right'caption='[[7bgc]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7bgc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BGC FirstGlance]. <br>		<table><tr><td colspan='2'>[[7bgc]] is a 1 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=7BGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BGC FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~"><~~scene name='pdbligand=CL:CHLORIDE+ION'~~>CL</~~scene~~>, <~~scene name~~='~~pdbligand~~=~~GOL~~:~~GLYCEROL'~~>~~GOL~~</~~scene~~>, <scene name='pdbligand=~~MES~~:~~2-(N-MORPHOLINO)-ETHANESULFONIC~~+~~ACID~~'>~~MES~~</scene>, <scene name='pdbligand=~~NAG~~:N-~~ACETYL~~-~~D-GLUCOSAMINE~~'>~~NAG~~</scene>, <scene name='pdbligand=~~SO4~~:~~SULFATE+ION~~'>~~SO4~~</scene>, <scene name='pdbligand=~~TKN~~:~~methyl+2-methoxy-6-[(~{E})-8-(1,2,3,4-tetrahydroacridin-9-ylamino)oct-6-enyl]benzoate~~'>~~TKN~~</scene>, <scene name='pdbligand=~~FUC~~:ALPHA-L-~~FUCOSE~~'>~~FUC~~</scene>, <scene name='pdbligand=~~GAL~~:~~BETA~~-D-~~GALACTOSE~~'>~~GAL~~</scene>, <scene name='pdbligand=~~MAN~~:~~ALPHA~~-D-~~MANNOSE~~'>~~MAN~~</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]] 2.4Å</td></tr>
	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene><~~/td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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>, <scene name='pdbligand=TKN:methyl+2-methoxy-6-[(~{E})-8-(1,2,3,4-tetrahydroacridin-9-ylamino)oct-6-enyl]benzoate'>TKN</scene></td></tr>
	~~<tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;~~'>~~[[1p0i\|1p0i]]~~</~~div~~><~~/td></tr>~~
	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks'>~~[~~https://en.wikipedia.org/wiki/Cholinesterase Cholinesterase], with EC number [https://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=3.~~1~~.1.8~~ 3~~.1.1.8~~] </~~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=7bgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bgc OCA], [https://pdbe.org/7bgc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bgc RCSB], [https://www.ebi.ac.uk/pdbsum/7bgc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bgc 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=7bgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bgc OCA], [https://pdbe.org/7bgc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bgc RCSB], [https://www.ebi.ac.uk/pdbsum/7bgc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bgc ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/CHLE_HUMAN CHLE_HUMAN]] Defects in BCHE are the cause of butyrylcholinesterase deficiency (BChE deficiency) [MIM:[https://omim.org/entry/177400 177400]]. BChE deficiency is a metabolic disorder characterized by prolonged apnoea after the use of certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anesthetics. The duration of the prolonged apnoea varies significantly depending on the extent of the enzyme deficiency. BChE deficiency is a multifactorial disorder. The hereditary condition is transmitted as an autosomal recessive trait.		[https://www.uniprot.org/uniprot/CHLE_HUMAN CHLE_HUMAN] Defects in BCHE are the cause of butyrylcholinesterase deficiency (BChE deficiency) [MIM:[https://omim.org/entry/177400 177400]. BChE deficiency is a metabolic disorder characterized by prolonged apnoea after the use of certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anesthetics. The duration of the prolonged apnoea varies significantly depending on the extent of the enzyme deficiency. BChE deficiency is a multifactorial disorder. The hereditary condition is transmitted as an autosomal recessive trait.
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/CHLE_HUMAN CHLE_HUMAN]] Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.<ref>PMID:19542320</ref> <ref>PMID:19452557</ref>		[https://www.uniprot.org/uniprot/CHLE_HUMAN CHLE_HUMAN] Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.<ref>PMID:19542320</ref> <ref>PMID:19452557</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7bgc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7bgc" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Butyrylcholinesterase 3D structures\|Butyrylcholinesterase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Cholinesterase~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Bolognesi~~, M L~~]]		[[Category: Bolognesi ML]]
	[[Category: Nachon, F]]		[[Category: Nachon F]]
	[[Category: Salerno, A]]		[[Category: Salerno A]]
	~~[[Category: Alzheimer]]~~
	~~[[Category: Anacardic acid]]~~
	~~[[Category: Butyrylcholinesterase]]~~
	~~[[Category: Hydrolase]]~~
	~~[[Category: Inhibitor]]~~
	~~[[Category: Tacrine~~]]

OCA at 09:07, 5 May 2021

2021-05-05T09:07:39Z

← Older revision		Revision as of 09:07, 5 May 2021
Line 1:		Line 1:

	==human butyrylcholinesterase in complex with a tacrine-methylanacardate hybrid inhibitor==		==human butyrylcholinesterase in complex with a tacrine-methylanacardate hybrid inhibitor==
	<StructureSection load='7bgc' size='340' side='right'caption='[[7bgc]]' scene=''>		<StructureSection load='7bgc' size='340' side='right'caption='[[7bgc]], [[Resolution\|resolution]] 2.40Å' 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=7BGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BGC FirstGlance]. <br>		<table><tr><td colspan='2'>[[7bgc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BGC 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=7bgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bgc OCA], [https://pdbe.org/7bgc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bgc RCSB], [https://www.ebi.ac.uk/pdbsum/7bgc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bgc ProSAT]</span></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TKN:methyl+2-methoxy-6-[(~{E})-8-(1,2,3,4-tetrahydroacridin-9-ylamino)oct-6-enyl]benzoate'>TKN</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
			<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1p0i\|1p0i]]</div></td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Cholinesterase Cholinesterase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.8 3.1.1.8] </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=7bgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bgc OCA], [https://pdbe.org/7bgc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bgc RCSB], [https://www.ebi.ac.uk/pdbsum/7bgc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bgc ProSAT]</span></td></tr>
	</table>		</table>
			== Disease ==
			[[https://www.uniprot.org/uniprot/CHLE_HUMAN CHLE_HUMAN]] Defects in BCHE are the cause of butyrylcholinesterase deficiency (BChE deficiency) [MIM:[https://omim.org/entry/177400 177400]]. BChE deficiency is a metabolic disorder characterized by prolonged apnoea after the use of certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anesthetics. The duration of the prolonged apnoea varies significantly depending on the extent of the enzyme deficiency. BChE deficiency is a multifactorial disorder. The hereditary condition is transmitted as an autosomal recessive trait.
			== Function ==
			[[https://www.uniprot.org/uniprot/CHLE_HUMAN CHLE_HUMAN]] Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.<ref>PMID:19542320</ref> <ref>PMID:19452557</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The multifactorial nature of Alzheimer's disease (AD) is a reason for the lack of effective drugs as well as a basis for the development of "multi-target-directed ligands" (MTDLs). As cases increase in developing countries, there is a need of new drugs that are not only effective but also accessible. With this motivation, we report the first sustainable MTDLs, derived from cashew nutshell liquid (CNSL), an inexpensive food waste with anti-inflammatory properties. We applied a framework combination of functionalized CNSL components and well-established acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) tacrine templates. MTDLs were selected based on hepatic, neuronal, and microglial cell toxicity. Enzymatic studies disclosed potent and selective AChE/BChE inhibitors (5, 6, and 12), with subnanomolar activities. The X-ray crystal structure of 5 complexed with BChE allowed rationalizing the observed activity (0.0352 nM). Investigation in BV-2 microglial cells revealed antineuroinflammatory and neuroprotective activities for 5 and 6 (already at 0.01 muM), confirming the design rationale.

			Sustainable Drug Discovery of Multi-Target-Directed Ligands for Alzheimer's Disease.,Rossi M, Freschi M, de Camargo Nascente L, Salerno A, de Melo Viana Teixeira S, Nachon F, Chantegreil F, Soukup O, Prchal L, Malaguti M, Bergamini C, Bartolini M, Angeloni C, Hrelia S, Soares Romeiro LA, Bolognesi ML J Med Chem. 2021 Apr 22;64(8):4972-4990. doi: 10.1021/acs.jmedchem.1c00048. Epub , 2021 Apr 8. PMID:33829779<ref>PMID:33829779</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7bgc" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Cholinesterase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Bolognesi ML]]		[[Category: Bolognesi, M L]]
	[[Category: Nachon F]]		[[Category: Nachon, F]]
	[[Category: Salerno A]]		[[Category: Salerno, A]]
			[[Category: Alzheimer]]
			[[Category: Anacardic acid]]
			[[Category: Butyrylcholinesterase]]
			[[Category: Hydrolase]]
			[[Category: Inhibitor]]
			[[Category: Tacrine]]

OCA at 05:19, 28 April 2021

2021-04-28T05:19:39Z

← Older revision		Revision as of 05:19, 28 April 2021
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The entry~~ 7bgc is ~~ON HOLD until Paper Publication~~		==human butyrylcholinesterase in complex with a tacrine-methylanacardate hybrid inhibitor==
			<StructureSection load='7bgc' size='340' side='right'caption='[[7bgc]]' scene=''>
	~~Authors~~: ~~Nachon~~, F., ~~Salerno~~, A., ~~Bolognesi~~, M.L.		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BGC FirstGlance]. <br>
	~~Description: human butyrylcholinesterase in complex with a tacrine-methylanacardate hybrid inhibitor~~		</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=7bgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bgc OCA], [https://pdbe.org/7bgc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bgc RCSB], [https://www.ebi.ac.uk/pdbsum/7bgc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bgc ProSAT]</span></td></tr>
	[[Category: ~~Unreleased~~ Structures]]		</table>
	[[Category: Bolognesi~~, M.L~~]]		__TOC__
	[[Category: ~~Salerno, A~~]]		</StructureSection>
	[[Category: ~~Nachon, F~~]]		[[Category: Large Structures]]
			[[Category: Bolognesi ML]]
			[[Category: Nachon F]]
			[[Category: Salerno A]]

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

2021-01-20T06:38:24Z

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

← Older revision	Revision as of 06:38, 20 January 2021
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7bgc is ON HOLD until Paper Publication Authors: Nachon, F., Salerno, A., Bolognesi, M.L. Description: human butyrylcholinesterase in complex with ...

2021-01-20T06:38:23Z

New page: '''Unreleased structure''' The entry 7bgc is ON HOLD until Paper Publication Authors: Nachon, F., Salerno, A., Bolognesi, M.L. Description: human butyrylcholinesterase in complex with ...

New page

'''Unreleased structure'''

The entry 7bgc is ON HOLD until Paper Publication

Authors: Nachon, F., Salerno, A., Bolognesi, M.L.

Description: human butyrylcholinesterase in complex with a tacrine-methylanacardate hybrid inhibitor
[[Category: Unreleased Structures]]
[[Category: Bolognesi, M.L]]
[[Category: Salerno, A]]
[[Category: Nachon, F]]