7awg - Revision history

OCA at 12:17, 1 February 2024

OCA — Thu, 01 Feb 2024 12:17:29 GMT

←Older revision		Revision as of 12:17, 1 February 2024
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	<StructureSection load='7awg' size='340' side='right'caption='[[7awg]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='7awg' size='340' side='right'caption='[[7awg]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7awg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AWG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7awg]] 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=7AWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AWG FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=S6Q:~{N}-(phenylmethyl)-2-[1-(phenylsulfonyl)indol-4-yl]oxy-ethanamine'>S6Q</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene~~>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</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]] 2Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</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=S6Q:~{N}-(phenylmethyl)-2-[1-(phenylsulfonyl)indol-4-yl]oxy-ethanamine'>S6Q</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=7awg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7awg OCA], [https://pdbe.org/7awg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7awg RCSB], [https://www.ebi.ac.uk/pdbsum/7awg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7awg 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=7awg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7awg OCA], [https://pdbe.org/7awg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7awg RCSB], [https://www.ebi.ac.uk/pdbsum/7awg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7awg 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 7awg" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7awg" 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: Brazzolotto, X]]	+	[[Category: Brazzolotto X]]
-	[[Category: Wichur, T]]	+	[[Category: Wichur T]]
-	[[Category: Wieckowska, A]]	+	[[Category: Wieckowska A]]
-	~~[[Category: Butyrylcholinesterase]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Inhibitor complex~~]]	+

OCA at 05:50, 6 October 2021

OCA — Wed, 06 Oct 2021 05:50:29 GMT

←Older revision		Revision as of 05:50, 6 October 2021
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	==Crystal structure of human butyrylcholinesterase in complex with (2-((1-(benzenesulfonyl)-1H-indol-4-yl)oxy)ethyl)(benzyl)amine==		==Crystal structure of human butyrylcholinesterase in complex with (2-((1-(benzenesulfonyl)-1H-indol-4-yl)oxy)ethyl)(benzyl)amine==
-	<StructureSection load='7awg' size='340' side='right'caption='[[7awg]]' scene=''>	+	<StructureSection load='7awg' size='340' side='right'caption='[[7awg]], [[Resolution\|resolution]] 2.00Å' 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=7AWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AWG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7awg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AWG 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=7awg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7awg OCA], [https://pdbe.org/7awg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7awg RCSB], [https://www.ebi.ac.uk/pdbsum/7awg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7awg 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=DMS:DIMETHYL+SULFOXIDE'>DMS</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=S6Q:~{N}-(phenylmethyl)-2-[1-(phenylsulfonyl)indol-4-yl]oxy-ethanamine'>S6Q</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></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=7awg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7awg OCA], [https://pdbe.org/7awg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7awg RCSB], [https://www.ebi.ac.uk/pdbsum/7awg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7awg 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 lack of an effective treatment makes Alzheimer's disease a serious healthcare problem and a challenge for medicinal chemists. Herein we report interdisciplinary research on novel multifunctional ligands targeting proteins and processes involved in the development of the disease: BuChE, 5-HT6 receptors and beta-amyloid aggregation. Structure-activity relationship analyses supported by crystallography and docking studies led to the identification of a fused-type multifunctional ligand 50, with remarkable and balanced potencies against BuChE (IC50 = 90 nM) and 5-HT6R (Ki = 4.8 nM), and inhibitory activity against Abeta aggregation (53% at 10 muM). In in vitro ADME-Tox and in vivo pharmacokinetic studies compound 50 showed good stability in the mouse liver microsomes, favourable safety profile and brain permeability with the brain to plasma ratio of 6.79 after p.o. administration in mice, thus being a promising candidate for in vivo pharmacology studies and a solid foundation for further research on effective anti-AD therapies.
		+
		+	Development and crystallography-aided SAR studies of multifunctional BuChE inhibitors and 5-HT6R antagonists with beta-amyloid anti-aggregation properties.,Wichur T, Godyn J, Goral I, Latacz G, Bucki A, Siwek A, Gluch-Lutwin M, Mordyl B, Sniecikowska J, Walczak M, Knez D, Jukic M, Salat K, Gobec S, Kolaczkowski M, Malawska B, Brazzolotto X, Wieckowska A Eur J Med Chem. 2021 Aug 27;225:113792. doi: 10.1016/j.ejmech.2021.113792. PMID:34530376<ref>PMID:34530376</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7awg" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Cholinesterase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Brazzolotto X]]	+	[[Category: Brazzolotto, X]]
-	[[Category: Wichur T]]	+	[[Category: Wichur, T]]
-	[[Category: Wieckowska A]]	+	[[Category: Wieckowska, A]]
		+	[[Category: Butyrylcholinesterase]]
		+	[[Category: Hydrolase]]
		+	[[Category: Inhibitor complex]]

OCA at 08:47, 29 September 2021

OCA — Wed, 29 Sep 2021 08:47:22 GMT

←Older revision		Revision as of 08:47, 29 September 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7awg is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of human butyrylcholinesterase in complex with (2-((1-(benzenesulfonyl)-1H-indol-4-yl)oxy)ethyl)(benzyl)amine==
-		+	<StructureSection load='7awg' size='340' side='right'caption='[[7awg]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AWG FirstGlance]. <br>
-	~~Description~~:	+	</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=7awg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7awg OCA], [https://pdbe.org/7awg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7awg RCSB], [https://www.ebi.ac.uk/pdbsum/7awg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7awg ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Brazzolotto X]]
		+	[[Category: Wichur T]]
		+	[[Category: Wieckowska A]]

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

OCA — Wed, 18 Nov 2020 07:53:51 GMT

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

←Older revision

Revision as of 07:53, 18 November 2020

OCA: New page: '''Unreleased structure''' The entry 7awg is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Wed, 18 Nov 2020 07:53:50 GMT

New page: '''Unreleased structure''' The entry 7awg is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7awg is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]