7amd - Revision history

OCA at 12:12, 1 February 2024

2024-02-01T12:12:07Z

← Older revision		Revision as of 12:12, 1 February 2024
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	<StructureSection load='7amd' size='340' side='right'caption='[[7amd]], [[Resolution\|resolution]] 2.25Å' scene=''>		<StructureSection load='7amd' size='340' side='right'caption='[[7amd]], [[Resolution\|resolution]] 2.25Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7amd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AMD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AMD FirstGlance]. <br>		<table><tr><td colspan='2'>[[7amd]] 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=7AMD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AMD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=RMW:[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-4-oxidanyl-3-phosphonooxy-oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(3~{R})-2,2-dimethyl-4-[[3-[2-[(1~{R})-2-(1-methylpyridin-4-yl)-1-naphthalen-1-yl-ethyl]sulfanylethylamino]-3-oxidanylidene-propyl]amino]-3-oxidanyl-4-oxidanylidene-butyl]+hydrogen+phosphate'>RMW</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]] 2.25Å</td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CHAT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=RMW:[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-4-oxidanyl-3-phosphonooxy-oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(3~{R})-2,2-dimethyl-4-[[3-[2-[(1~{R})-2-(1-methylpyridin-4-yl)-1-naphthalen-1-yl-ethyl]sulfanylethylamino]-3-oxidanylidene-propyl]amino]-3-oxidanyl-4-oxidanylidene-butyl]+hydrogen+phosphate'>RMW</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Choline_O-acetyltransferase Choline O-acetyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.6 2.3.1.6] </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=7amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7amd OCA], [https://pdbe.org/7amd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7amd RCSB], [https://www.ebi.ac.uk/pdbsum/7amd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7amd 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=7amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7amd OCA], [https://pdbe.org/7amd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7amd RCSB], [https://www.ebi.ac.uk/pdbsum/7amd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7amd ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/CLAT_HUMAN CLAT_HUMAN]] Defects in CHAT are the cause of congenital myasthenic syndrome with episodic apnea (CMSEA) [MIM:[https://omim.org/entry/254210 254210]]; formerly known as familial infantile myasthenia gravis 2 (FIMG2). CMSEA is an autosomal recessive congenital myasthenic syndrome. Patients have myasthenic symptoms since birth or early infancy, negative tests for anti-AChR antibodies, and abrupt episodic crises with increased weakness, bulbar paralysis, and apnea precipitated by undue exertion, fever, or excitement.<ref>PMID:11172068</ref> <ref>PMID:12756141</ref>		[https://www.uniprot.org/uniprot/CLAT_HUMAN CLAT_HUMAN] Defects in CHAT are the cause of congenital myasthenic syndrome with episodic apnea (CMSEA) [MIM:[https://omim.org/entry/254210 254210]; formerly known as familial infantile myasthenia gravis 2 (FIMG2). CMSEA is an autosomal recessive congenital myasthenic syndrome. Patients have myasthenic symptoms since birth or early infancy, negative tests for anti-AChR antibodies, and abrupt episodic crises with increased weakness, bulbar paralysis, and apnea precipitated by undue exertion, fever, or excitement.<ref>PMID:11172068</ref> <ref>PMID:12756141</ref>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/CLAT_HUMAN CLAT_HUMAN]] Catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses.		[https://www.uniprot.org/uniprot/CLAT_HUMAN CLAT_HUMAN] Catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses.
	<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 7amd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7amd" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Choline O-acetyltransferase\|Choline O-acetyltransferase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Choline O-acetyltransferase]]~~		[[Category: Homo sapiens]]
	~~[[Category: Human~~]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Akfur, C]]		[[Category: Akfur C]]
	[[Category: Allgardsson, A]]		[[Category: Allgardsson A]]
	[[Category: Bergstrom, T]]		[[Category: Bergstrom T]]
	[[Category: Ekstrom~~, F J~~]]		[[Category: Ekstrom FJ]]
	[[Category: Forsgren, N]]		[[Category: Forsgren N]]
	[[Category: Hedenstrom, M]]		[[Category: Hedenstrom M]]
	[[Category: Hoster, N]]		[[Category: Hoster N]]
	[[Category: Lejon, C]]		[[Category: Lejon C]]
	[[Category: Linusson, A]]		[[Category: Linusson A]]
	[[Category: Wiktelius, D]]		[[Category: Wiktelius D]]
	~~[[Category: Avp]]~~
	~~[[Category: Chat]]~~
	~~[[Category: Hydrothiolation]]~~
	~~[[Category: Inhibitor]]~~
	~~[[Category: Transferase~~]]

OCA at 15:00, 3 March 2021

2021-03-03T15:00:55Z

← Older revision		Revision as of 15:00, 3 March 2021
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	==In situ assembly of choline acetyltransferase ligands by a hydrothiolation reaction reveals key determinants for inhibitor design==		==In situ assembly of choline acetyltransferase ligands by a hydrothiolation reaction reveals key determinants for inhibitor design==
	<StructureSection load='7amd' size='340' side='right'caption='[[7amd]]' scene=''>		<StructureSection load='7amd' size='340' side='right'caption='[[7amd]], [[Resolution\|resolution]] 2.25Å' 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=7AMD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7AMD FirstGlance]. <br>		<table><tr><td colspan='2'>[[7amd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AMD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AMD FirstGlance]. <br>
	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=7amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7amd OCA], [~~http~~://pdbe.org/7amd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7amd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7amd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7amd 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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=RMW:[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-4-oxidanyl-3-phosphonooxy-oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(3~{R})-2,2-dimethyl-4-[[3-[2-[(1~{R})-2-(1-methylpyridin-4-yl)-1-naphthalen-1-yl-ethyl]sulfanylethylamino]-3-oxidanylidene-propyl]amino]-3-oxidanyl-4-oxidanylidene-butyl]+hydrogen+phosphate'>RMW</scene></td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CHAT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Choline_O-acetyltransferase Choline O-acetyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.6 2.3.1.6] </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=7amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7amd OCA], [https://pdbe.org/7amd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7amd RCSB], [https://www.ebi.ac.uk/pdbsum/7amd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7amd ProSAT]</span></td></tr>
	</table>		</table>
			== Disease ==
			[[https://www.uniprot.org/uniprot/CLAT_HUMAN CLAT_HUMAN]] Defects in CHAT are the cause of congenital myasthenic syndrome with episodic apnea (CMSEA) [MIM:[https://omim.org/entry/254210 254210]]; formerly known as familial infantile myasthenia gravis 2 (FIMG2). CMSEA is an autosomal recessive congenital myasthenic syndrome. Patients have myasthenic symptoms since birth or early infancy, negative tests for anti-AChR antibodies, and abrupt episodic crises with increased weakness, bulbar paralysis, and apnea precipitated by undue exertion, fever, or excitement.<ref>PMID:11172068</ref> <ref>PMID:12756141</ref>
			== Function ==
			[[https://www.uniprot.org/uniprot/CLAT_HUMAN CLAT_HUMAN]] Catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The potential drug target choline acetyltransferase (ChAT) catalyzes the production of the neurotransmitter acetylcholine in cholinergic neurons, T-cells, and B-cells. Herein, we show that arylvinylpyridiniums (AVPs), the most widely studied class of ChAT inhibitors, act as substrate in an unusual coenzyme A-dependent hydrothiolation reaction. This in-situ synthesis yields an adduct that is the actual enzyme inhibitor. The adduct is deeply buried in the active site tunnel of ChAT and interactions with a hydrophobic pocket near the choline binding site have major implications for the molecular recognition of inhibitors. Our findings clarify the inhibition mechanism of AVPs, establish a drug modality that exploits a target-catalysed reaction between exogenous and endogenous precursors, and provide new directions for the development of ChAT inhibitors with improved potency and bioactivity.

			In situ assembly of choline acetyltransferase ligands by a hydrothiolation reaction reveals key determinants for inhibitor design.,Wiktelius D, Allgardsson A, Bergstrom T, Hoster N, Akfur C, Forsgren N, Lejon C, Hedenstrom M, Linusson A, Ekstrom F Angew Chem Int Ed Engl. 2020 Oct 20. doi: 10.1002/anie.202011989. PMID:33079431<ref>PMID:33079431</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7amd" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Choline O-acetyltransferase]]
			[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Akfur C]]		[[Category: Akfur, C]]
	[[Category: Allgardsson A]]		[[Category: Allgardsson, A]]
	[[Category: Bergstrom T]]		[[Category: Bergstrom, T]]
	[[Category: Ekstrom FJ]]		[[Category: Ekstrom, F J]]
	[[Category: Forsgren N]]		[[Category: Forsgren, N]]
	[[Category: Hedenstrom M]]		[[Category: Hedenstrom, M]]
	[[Category: Hoster N]]		[[Category: Hoster, N]]
	[[Category: Lejon C]]		[[Category: Lejon, C]]
	[[Category: Linusson A]]		[[Category: Linusson, A]]
	[[Category: Wiktelius D]]		[[Category: Wiktelius, D]]
			[[Category: Avp]]
			[[Category: Chat]]
			[[Category: Hydrothiolation]]
			[[Category: Inhibitor]]
			[[Category: Transferase]]

OCA at 20:37, 28 October 2020

2020-10-28T20:37:03Z

← Older revision		Revision as of 20:37, 28 October 2020
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	~~'''Unreleased structure'''~~

	~~The entry~~ 7amd is ~~ON HOLD until Paper Publication~~		==In situ assembly of choline acetyltransferase ligands by a hydrothiolation reaction reveals key determinants for inhibitor design==
			<StructureSection load='7amd' size='340' side='right'caption='[[7amd]]' scene=''>
	~~Authors~~:		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AMD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7AMD FirstGlance]. <br>
	~~Description~~:		</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7amd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7amd OCA], [http://pdbe.org/7amd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7amd RCSB], [http://www.ebi.ac.uk/pdbsum/7amd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7amd ProSAT]</span></td></tr>
	[[Category: ~~Unreleased Structures~~]]		</table>
			__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: Akfur C]]
			[[Category: Allgardsson A]]
			[[Category: Bergstrom T]]
			[[Category: Ekstrom FJ]]
			[[Category: Forsgren N]]
			[[Category: Hedenstrom M]]
			[[Category: Hoster N]]
			[[Category: Lejon C]]
			[[Category: Linusson A]]
			[[Category: Wiktelius D]]

OCA at 06:35, 21 October 2020

2020-10-21T06:35:32Z

← Older revision		Revision as of 06:35, 21 October 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7amd is ON HOLD		The entry 7amd is ON HOLD until Paper Publication

	Authors:		Authors:

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

2020-10-14T04:06:30Z

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

← Older revision	Revision as of 04:06, 14 October 2020
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7amd is ON HOLD Authors: Description: Category: Unreleased Structures

2020-10-14T04:06:29Z

New page: '''Unreleased structure''' The entry 7amd is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7amd is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]