5moy - Revision history

OCA at 17:42, 8 November 2023

OCA — Wed, 08 Nov 2023 17:42:37 GMT

←Older revision		Revision as of 17:42, 8 November 2023
Line 3:		Line 3:
	<StructureSection load='5moy' size='340' side='right'caption='[[5moy]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='5moy' size='340' side='right'caption='[[5moy]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5moy]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896~~] and [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MOY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5MOY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5moy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MOY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MOY FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>~~, ~~<scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 2.302Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>~~[[~~Related_structure~~\|~~Related:]]</b></td><td class="sblockDat">[[4jra\|4jra~~]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>botA, atx, bna ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~1491~~ "~~Bacillus botulinus~~" ~~van Ermengem 1896]), SV2C, KIAA1054 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5moy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5moy OCA], [https://pdbe.org/5moy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5moy RCSB], [https://www.ebi.ac.uk/pdbsum/5moy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5moy ProSAT]</span></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[http~~:~~//en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin]~~, ~~with EC number [http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=3.4.24.69 3.4.24.69]~~ </~~span~~></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=5moy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5moy OCA], [~~http~~://pdbe.org/5moy PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5moy RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5moy PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5moy ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~BXA2_CLOBO BXA2_CLOBO~~]~~] Inhibits~~ acetylcholine release~~. The botulinum toxin binds with high affinity to peripheral neuronal~~ presynaptic ~~membrane to the secretory vesicle protein SV2. It binds directly to the largest luminal loop~~ of ~~the three isoforms SV2A~~, ~~SV2B and SV2C~~. ~~It is then internalized by receptor~~-~~mediated endocytosis~~. ~~The C-terminus of~~ the heavy chain (H) is ~~responsible for~~ the ~~adherence~~ of the toxin ~~to the cell surface while~~ the N-terminus ~~mediates transport~~ of the light chain ~~from the endocytic vesicle~~ to the cytosol. ~~After translocation~~, the ~~light chain~~ (L) hydrolyzes the '197-Gln-\|-Arg-198' bond in ~~SNAP-25~~, ~~thereby~~ blocking neurotransmitter release~~. Inhibition of acetylcholine release results in flaccid paralysis, with frequent heart or respiratory failure~~ (~~By similarity~~). ~~[[http~~:/~~/www~~.~~uniprot~~.~~org/uniprot/SV2C_HUMAN SV2C_HUMAN]] Plays a role in~~ the ~~control~~ of ~~regulated secretion in neural~~ and ~~endocrine cells~~, ~~enhancing selectively low~~-~~frequency neurotransmission~~. ~~Positively regulates~~ vesicle ~~fusion by maintaining~~ the ~~readily releasable pool of secretory vesicles~~ (By similarity).	+	[https://www.uniprot.org/uniprot/BXA2_CLOBJ BXA2_CLOBJ] Botulinum toxin causes flaccid paralysis by inhibiting neurotransmitter (acetylcholine) release from the presynaptic membranes of nerve terminals of eukaryotic host skeletal and autonomic nervous system, with frequent heart or respiratory failure. Precursor of botulinum neurotoxin A2 which has 2 coreceptors; complex polysialylated gangliosides found on neural tissue and specific membrane-anchored proteins found in synaptic vesicles. Receptor proteins are exposed on host presynaptic cell membrane during neurotransmitter release, when the toxin heavy chain (HC) binds to them. Upon synaptic vesicle recycling the toxin is taken up via the endocytic pathway. When the pH of the toxin-containing endosome drops a structural rearrangement occurs so that the N-terminus of the HC forms pores that allows the light chain (LC) to translocate into the cytosol. Once in the cytosol the disulfide bond linking the 2 subunits is reduced and LC cleaves its target protein on synaptic vesicles, preventing their fusion with the cytoplasmic membrane and thus neurotransmitter release (By similarity).[UniProtKB:P0DPI0] Has proteolytic activity. After translocation into the eukaryotic host cytosol, LC hydrolyzes the 197-Gln-\|-Arg-198 bond in SNAP25, blocking neurotransmitter release (PubMed:16846233).<ref>PMID:16846233</ref> Responsible for host epithelial cell transcytosis, host nerve cell targeting and translocation of light chain (LC) into host cytosol. Composed of 3 subdomains; the translocation domain (TD), and N-terminus and C-terminus of the receptor-binding domain (RBD). The RBD is responsible for the adherence of the toxin to the cell surface. It simultaneously recognizes 2 coreceptors; polysialated gangliosides and the receptor protein SV2 in close proximity on host synaptic vesicles (PubMed:28252640, PubMed:29649119). The N-terminus of the TD wraps an extended belt around the perimeter of the LC, protecting Zn(2+) in the active site; it may also prevent premature LC dissociation from the translocation channel and to protect toxin prior to translocation (By similarity). The TD inserts into synaptic vesicle membrane to allow translocation into the host cytosol (By similarity).[UniProtKB:P0DPI0]<ref>PMID:28252640</ref> <ref>PMID:29649119</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bacillus botulinus van ermengem 1896~~]]	+	[[Category: Clostridium botulinum]]
-	[[Category: ~~Bontoxilysin]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Benoit~~, R M~~]]	+	[[Category: Benoit RM]]
-	[[Category: Scharer~~, M A]]~~	+	[[Category: Scharer MA]]
-	~~[[Category: Beta-helix]]~~	+
-	~~[[Category: Botox]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Lumen]]~~	+
-	~~[[Category: Toxin]]~~	+
-	~~[[Category: Vesicle~~]]	+

OCA at 07:25, 19 August 2020

OCA — Wed, 19 Aug 2020 07:25:42 GMT

←Older revision		Revision as of 07:25, 19 August 2020
Line 1:		Line 1:

	==Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C==		==Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C==
-	<StructureSection load='5moy' size='340' side='right' caption='[[5moy]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='5moy' size='340' side='right'caption='[[5moy]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5moy]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MOY OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5MOY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5moy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MOY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MOY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jra\|4jra]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jra\|4jra]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">botA, atx, bna ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 "Bacillus botulinus" van Ermengem 1896]), SV2C, KIAA1054 ([http://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'>[http://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.69 3.4.24.69] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.69 3.4.24.69] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5moy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5moy OCA], [http://pdbe.org/5moy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5moy RCSB], [http://www.ebi.ac.uk/pdbsum/5moy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5moy ProSAT]</span></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=5moy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5moy OCA], [http://pdbe.org/5moy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5moy RCSB], [http://www.ebi.ac.uk/pdbsum/5moy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5moy ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5moy" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5moy" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Botulinum neurotoxin 3D structures\|Botulinum neurotoxin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bacillus botulinus van ermengem 1896]]
	[[Category: Bontoxilysin]]		[[Category: Bontoxilysin]]
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Benoit, R M]]		[[Category: Benoit, R M]]
	[[Category: Scharer, M A]]		[[Category: Scharer, M A]]

OCA at 21:11, 15 March 2017

OCA — Wed, 15 Mar 2017 21:11:59 GMT

←Older revision		Revision as of 21:11, 15 March 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5moy is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C==
		+	<StructureSection load='5moy' size='340' side='right' caption='[[5moy]], [[Resolution\|resolution]] 2.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5moy]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MOY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MOY FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jra\|4jra]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.69 3.4.24.69] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5moy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5moy OCA], [http://pdbe.org/5moy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5moy RCSB], [http://www.ebi.ac.uk/pdbsum/5moy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5moy ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BXA2_CLOBO BXA2_CLOBO]] Inhibits acetylcholine release. The botulinum toxin binds with high affinity to peripheral neuronal presynaptic membrane to the secretory vesicle protein SV2. It binds directly to the largest luminal loop of the three isoforms SV2A, SV2B and SV2C. It is then internalized by receptor-mediated endocytosis. The C-terminus of the heavy chain (H) is responsible for the adherence of the toxin to the cell surface while the N-terminus mediates transport of the light chain from the endocytic vesicle to the cytosol. After translocation, the light chain (L) hydrolyzes the '197-Gln-\|-Arg-198' bond in SNAP-25, thereby blocking neurotransmitter release. Inhibition of acetylcholine release results in flaccid paralysis, with frequent heart or respiratory failure (By similarity). [[http://www.uniprot.org/uniprot/SV2C_HUMAN SV2C_HUMAN]] Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily releasable pool of secretory vesicles (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A detailed molecular understanding of botulinum neurotoxin (BoNT)/host-cell-receptor interactions is fundamental both for developing strategies against botulism and for generating improved BoNT variants for medical applications. The X-ray crystal structure of the receptor-binding domain (HC) of BoNT/A1 in complex with the luminal domain (LD) of its neuronal receptor SV2C revealed only few specific side-chain - side-chain interactions that are important for binding. Notably, two BoNT/A1 residues, Arg 1156 and Arg 1294, that are crucial for the interaction with SV2, are not conserved among subtypes. Because it has been suggested that differential receptor binding of subtypes might explain their differences in biological activity, we determined the crystal structure of BoNT/A2-HC in complex with SV2C-LD. Although only few side-chain interactions are conserved between the two BoNT/A subtypes, the overall binding mode of subtypes A1 and A2 is virtually identical. In the BoNT/A2-HC - SV2C complex structure, a missing cation-pi stacking is compensated for by an additional salt bridge and an anion-pi stacking interaction, which explains why the binding of BoNT/A subtypes to SV2C tolerates variable side chains. These findings suggest that motif extensions and a shallow binding cleft in BoNT/A-HC contribute to binding specificity.

-	~~Authors~~:	+	Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C.,Benoit RM, Scharer MA, Wieser MM, Li X, Frey D, Kammerer RA Sci Rep. 2017 Mar 2;7:43588. doi: 10.1038/srep43588. PMID:28252640<ref>PMID:28252640</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5moy" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Bontoxilysin]]
		+	[[Category: Benoit, R M]]
		+	[[Category: Scharer, M A]]
		+	[[Category: Beta-helix]]
		+	[[Category: Botox]]
		+	[[Category: Hydrolase]]
		+	[[Category: Lumen]]
		+	[[Category: Toxin]]
		+	[[Category: Vesicle]]

OCA at 13:48, 2 January 2017

OCA — Mon, 02 Jan 2017 13:48:24 GMT

←Older revision		Revision as of 13:48, 2 January 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5moy is ON HOLD	+	The entry 5moy is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "5moy" [edit=sysop:move=sysop]

OCA — Thu, 22 Dec 2016 19:16:26 GMT

Protected "5moy" [edit=sysop:move=sysop]

←Older revision

Revision as of 19:16, 22 December 2016

OCA: New page: '''Unreleased structure''' The entry 5moy is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Thu, 22 Dec 2016 19:16:25 GMT

New page: '''Unreleased structure''' The entry 5moy is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5moy is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]