3r4s - Revision history

OCA at 10:52, 21 February 2024

OCA — Wed, 21 Feb 2024 10:52:19 GMT

←Older revision		Revision as of 10:52, 21 February 2024
Line 3:		Line 3:
	<StructureSection load='3r4s' size='340' side='right'caption='[[3r4s]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='3r4s' size='340' side='right'caption='[[3r4s]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3r4s]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~"bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R4S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R4S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3r4s]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R4S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R4S FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=SIA:O~~-~~SIALIC+ACID'>SIA</scene>~~, ~~<scene name='pdbligand=SLB:5-N-ACETYL-BETA-D-NEURAMINIC+ACID'>SLB</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]] 2.15Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;~~'>~~[[3r4u\|3r4u]]~~</~~div~~><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=SLB:5-N-ACETYL-BETA-D-NEURAMINIC+ACID'>SLB</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks~~'>~~[https://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3r4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r4s OCA], [https://pdbe.org/3r4s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r4s RCSB], [https://www.ebi.ac.uk/pdbsum/3r4s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r4s 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=3r4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r4s OCA], [https://pdbe.org/3r4s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r4s RCSB], [https://www.ebi.ac.uk/pdbsum/3r4s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r4s ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/~~BXC1_CLOBO BXC1_CLOBO]~~] Botulinum toxin ~~acts~~ by inhibiting neurotransmitter release. ~~It binds~~ to ~~peripheral neuronal synapses~~, ~~is internalized~~ and ~~moves by retrograde transport~~ up the ~~axon~~ into the ~~spinal cord where it can move between postsynaptic~~ and ~~presynaptic neurons~~. It inhibits neurotransmitter release by acting as a zinc endopeptidase that cleaves syntaxin.	+	[https://www.uniprot.org/uniprot/BXC_CBCP BXC_CBCP] Botulinum toxin causes flaccid paralysis by inhibiting neurotransmitter (acetylcholine) release from the presynaptic membranes of nerve terminals of the eukaryotic host skeletal and autonomic nervous system, with frequent heart or respiratory failure (PubMed:16252491, PubMed:7901002, PubMed:8611567). Is unique among characterized BoNTs in having 2 substrates, syntaxin (STX) and SNAP25 (PubMed:7901002, PubMed:7737992, PubMed:8611567, PubMed:9886085, PubMed:17718519). Precursor of botulinum neurotoxin C which unlike most BoNTs seems not to have a proteinaceous coreceptor, and instead recognizes 2 different complex polysialylated gangliosides found on neural tissue probably found in synaptic vesicles (PubMed:21483489, PubMed:23027864). 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 heavy chain (HC) forms pores that allows the light chain (LC) to translocate into the cytosol (By similarity). 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). In vitro the whole toxin only has protease activity after reduction (PubMed:8611567). Electrical stimulation increases uptake of toxin, presumably by transiently exposing a receptor usually found in eukaryotic target synaptic vesicles (PubMed:19650874). Forms ion-conducting channels at around pH 6.1 (PubMed:2424493). Requires complex eukaryotic host polysialogangliosides for full neurotoxicity (PubMed:19650874, PubMed:21483489). Synaptic vesicle glycoproteins (SV2) do not seem to act as its receptor (PubMed:21483489).[UniProtKB:P0DPI0]<ref>PMID:17718519</ref> <ref>PMID:19650874</ref> <ref>PMID:21483489</ref> <ref>PMID:2424493</ref> <ref>PMID:7737992</ref> <ref>PMID:7901002</ref> <ref>PMID:8611567</ref> <ref>PMID:9886085</ref> <ref>PMID:16252491</ref> <ref>PMID:23027864</ref> Has proteolytic activity. After translocation into the eukaryotic host cytosol, inhibits neurotransmitter release by acting as a zinc endopeptidase that cleaves syntaxin-1A/STX1A and syntaxin-1B/STX1B (PubMed:7901002, PubMed:7737992, PubMed:8611567). Cleaves the '253-Arg-\|-Ala-254' bond of STX1 and the '252-Arg-\|-Ala-253' bond of STX2; also acts on syntaxin 3 (STX3) but not 4 (STX4) (PubMed:7737992). Cleaves the '198-Arg-\|-Ala-199' bond of SNAP25 (PubMed:8611567, PubMed:9886085, PubMed:17718519). Recognizes the '93-Asn--Met-202' region of SNAP25 (PubMed:9886085).<ref>PMID:17718519</ref> <ref>PMID:7737992</ref> <ref>PMID:7901002</ref> <ref>PMID:8611567</ref> <ref>PMID:9886085</ref> Responsible for host epithelial cell transcytosis, host nerve cell targeting and translocation of light chain (LC) into eukaryotic 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 eukaryotic target cell surface. It simultaneously recognizes 2 polysialated gangliosides coreceptors in close proximity on host synaptic vesicles (PubMed:23027864, PubMed:21542861). 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 protect toxin prior to translocation (By similarity). The TD inserts into synaptic vesicle membrane to allow translocation into the host cytosol (Probable). The C-terminal half of the HC (residues 864-1291) binds neurons in a dose-dependent manner (PubMed:20731382). The C-terminal half of the HC (residues 863-1291) binds eukaryotic host gangliosides in the order GD1b > GT1b > GD1a > GM1a (PubMed:16115873, PubMed:20731382, PubMed:23027864, PubMed:19650874). Has 2 ganglioside binding sites; Sia-1 prefers a sia7 sialic acid and sugars within the ganglioside (GD1b > GT1b), whereas GBP2 recognizes a sia5 sialic acid (GT1b and GD1a) (PubMed:23027864, PubMed:21542861). Both sites are required for HC to enter neurons, acting via different gangliosides (PubMed:23027864). This suggests that 2 gangliosides serve as toxin receptors (PubMed:16115873, PubMed:20731382, PubMed:21542861, PubMed:23027864). Synaptic activity (depolarization with K(+)) increases uptake by neurons (PubMed:23027864). Treatment of synaptosomes with proteinase K does not reduce HC binding, suggesting there is no protein receptor or it is protected from extracellular proteases (PubMed:16115873). Decreases uptake and toxicity of whole BoNT/A, but also interferes with uptake of BoNT/E and BoNT/F (PubMed:19650874). HC also binds phosphoinositides, which might play a role in membrane-binding (PubMed:22120109).[UniProtKB:P0DPI0]<ref>PMID:16115873</ref> <ref>PMID:19650874</ref> <ref>PMID:20731382</ref> <ref>PMID:21542861</ref> <ref>PMID:22120109</ref> <ref>PMID:23027864</ref> <ref>PMID:2424493</ref>
-	~~<div style="background~~-~~color~~:~~#fffaf0;">~~	+
-	~~== Publication Abstract from~~ PubMed ==	+
-	~~The seven botulinum neurotoxins (BoNT~~) ~~cause muscle paralysis by selectively cleaving core components~~ of the ~~vesicular fusion machinery. Their extraordinary activity primarily relies~~ on ~~highly specific entry into neurons~~. ~~Data on BoNT/A~~, B, E, F and ~~G suggest that entry follows a dual~~ receptor ~~interaction with complex gangliosides via an established ganglioside~~ binding ~~region and a synaptic vesicle protein~~. ~~Here, we report high resolution crystal structures~~ of the ~~BoNT/C~~ cell ~~binding fragment alone and~~ in ~~complex with sialic acid~~. The WY-~~motif characteristic~~ of the ~~established ganglioside binding region was located on~~ an ~~exposed loop. Sialic acid was co-ordinated at a novel position neighbouring~~ the ~~binding pocket for synaptotagmin~~ in ~~BoNT/B and G and~~ the ~~sialic acid binding~~ site ~~in BoNT/D~~ and ~~TeNT respectively~~. ~~Employing synaptosomes and immobilized gangliosides binding studies with BoNT/C mutants showed that~~ the ~~ganglioside binding WY~~-~~loop,~~ the ~~newly identified sialic acid~~-co-~~ordinating pocket and the area corresponding to the established ganglioside binding region~~ of ~~other BoNTs are involved~~ in ~~ganglioside interaction~~. ~~Phrenic nerve hemidiaphragm activity tests employing~~ ganglioside ~~deficient mice furthermore evidenced that the biological activity of BoNT/C depends on ganglioside interaction with at least two~~ binding sites~~. These data suggest~~ a ~~unique cell binding~~ and ~~entry mechanism for BoNT/C among clostridial neurotoxins.~~	+
-		+
-	~~The biological activity of botulinum neurotoxin type C is dependent upon novel types of~~ ganglioside ~~binding sites.~~,~~Strotmeier J~~, ~~Gu S~~, ~~Jutzi S~~, ~~Mahrhold S~~, ~~Zhou J~~, ~~Pich A, Eichner T, Bigalke H, Rummel A, Jin R, Binz T Mol Microbiol~~. ~~2011 May 4~~. ~~doi~~: 10.~~1111~~/j.~~1365~~-~~2958.2011.07682.x~~. PMID:~~21542861~~<ref>PMID:~~21542861~~</ref>	+
-		+
-	~~From MEDLINE®~~/~~PubMed®, a database of the U.S. National Library of Medicine.~~<br>	+
-	</~~div~~>	+
-	<~~div class="pdbe-citations 3r4s" style="background-color~~:~~#fffaf0;"~~></~~div~~>	+

	==See Also==		==See Also==
Line 27:		Line 17:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bacillus botulinus van ermengem 1896]]~~	+	[[Category: Clostridium botulinum]]
-	~~[[Category: Bontoxilysin~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bigalke, H]]	+	[[Category: Bigalke H]]
-	[[Category: Binz, T]]	+	[[Category: Binz T]]
-	[[Category: Gu, S]]	+	[[Category: Gu S]]
-	[[Category: Jin, R]]	+	[[Category: Jin R]]
-	[[Category: Jutzi, S]]	+	[[Category: Jutzi S]]
-	[[Category: Mahrhold, S]]	+	[[Category: Mahrhold S]]
-	[[Category: Pich, A]]	+	[[Category: Pich A]]
-	[[Category: Rummel, A]]	+	[[Category: Rummel A]]
-	[[Category: Strotmeier, J]]	+	[[Category: Strotmeier J]]
-	[[Category: Zhou, J]]	+	[[Category: Zhou J]]
-	~~[[Category: Botulinum toxin]]~~	+
-	~~[[Category: Ganglioside]]~~	+
-	~~[[Category: Hydrolase~~]]	+

OCA at 05:48, 15 June 2022

OCA — Wed, 15 Jun 2022 05:48:55 GMT

←Older revision		Revision as of 05:48, 15 June 2022
Line 3:		Line 3:
	<StructureSection load='3r4s' size='340' side='right'caption='[[3r4s]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='3r4s' size='340' side='right'caption='[[3r4s]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3r4s]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/"bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R4S OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3R4S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3r4s]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R4S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R4S FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=SLB:5-N-ACETYL-BETA-D-NEURAMINIC+ACID'>SLB</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=SLB:5-N-ACETYL-BETA-D-NEURAMINIC+ACID'>SLB</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3r4u\|3r4u]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3r4u\|3r4u]]</div></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'>[https://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [https://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=3r4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r4s OCA], [~~http~~://pdbe.org/3r4s PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3r4s RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3r4s PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3r4s 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=3r4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r4s OCA], [https://pdbe.org/3r4s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r4s RCSB], [https://www.ebi.ac.uk/pdbsum/3r4s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r4s ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/BXC1_CLOBO BXC1_CLOBO]] Botulinum toxin acts by inhibiting neurotransmitter release. It binds to peripheral neuronal synapses, is internalized and moves by retrograde transport up the axon into the spinal cord where it can move between postsynaptic and presynaptic neurons. It inhibits neurotransmitter release by acting as a zinc endopeptidase that cleaves syntaxin.	+	[[https://www.uniprot.org/uniprot/BXC1_CLOBO BXC1_CLOBO]] Botulinum toxin acts by inhibiting neurotransmitter release. It binds to peripheral neuronal synapses, is internalized and moves by retrograde transport up the axon into the spinal cord where it can move between postsynaptic and presynaptic neurons. It inhibits neurotransmitter release by acting as a zinc endopeptidase that cleaves syntaxin.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 13:58, 25 December 2019

OCA — Wed, 25 Dec 2019 13:58:56 GMT

←Older revision		Revision as of 13:58, 25 December 2019
Line 1:		Line 1:

	==Cell entry of botulinum neurotoxin type C is dependent upon interaction with two ganglioside molecules==		==Cell entry of botulinum neurotoxin type C is dependent upon interaction with two ganglioside molecules==
-	<StructureSection load='3r4s' size='340' side='right' caption='[[3r4s]], [[Resolution\|resolution]] 2.15Å' scene=''>	+	<StructureSection load='3r4s' size='340' side='right'caption='[[3r4s]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3r4s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R4S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R4S FirstGlance]. <br>		<table><tr><td colspan='2'>[[3r4s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R4S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R4S FirstGlance]. <br>
Line 22:		Line 22:

	==See Also==		==See Also==
-	*[[Botulinum neurotoxin\|Botulinum neurotoxin]]	+	*[[Botulinum neurotoxin 3D structures\|Botulinum neurotoxin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 29:
	[[Category: Bacillus botulinus van ermengem 1896]]		[[Category: Bacillus botulinus van ermengem 1896]]
	[[Category: Bontoxilysin]]		[[Category: Bontoxilysin]]
		+	[[Category: Large Structures]]
	[[Category: Bigalke, H]]		[[Category: Bigalke, H]]
	[[Category: Binz, T]]		[[Category: Binz, T]]

OCA at 13:44, 5 August 2016

OCA — Fri, 05 Aug 2016 13:44:57 GMT

←Older revision		Revision as of 13:44, 5 August 2016
Line 1:		Line 1:
		+
	==Cell entry of botulinum neurotoxin type C is dependent upon interaction with two ganglioside molecules==		==Cell entry of botulinum neurotoxin type C is dependent upon interaction with two ganglioside molecules==
	<StructureSection load='3r4s' size='340' side='right' caption='[[3r4s]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='3r4s' size='340' side='right' caption='[[3r4s]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3r4s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Clostridium_botulinum Clostridium botulinum~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R4S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R4S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3r4s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R4S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R4S FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=SLB:5-N-ACETYL-BETA-D-NEURAMINIC+ACID'>SLB</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=SLB:5-N-ACETYL-BETA-D-NEURAMINIC+ACID'>SLB</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3r4u\|3r4u]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3r4u\|3r4u]]</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=3r4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r4s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r4s RCSB], [http://www.ebi.ac.uk/pdbsum/3r4s PDBsum]</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=3r4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r4s OCA], [http://pdbe.org/3r4s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3r4s RCSB], [http://www.ebi.ac.uk/pdbsum/3r4s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3r4s ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3r4s" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Botulinum neurotoxin\|Botulinum neurotoxin]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Bacillus botulinus van ermengem 1896]]
	[[Category: Bontoxilysin]]		[[Category: Bontoxilysin]]
-	[[Category: Clostridium botulinum]]
	[[Category: Bigalke, H]]		[[Category: Bigalke, H]]
	[[Category: Binz, T]]		[[Category: Binz, T]]

OCA at 02:59, 25 December 2014

OCA — Thu, 25 Dec 2014 02:59:13 GMT

←Older revision		Revision as of 02:59, 25 December 2014
Line 8:		Line 8:
	<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=3r4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r4s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r4s RCSB], [http://www.ebi.ac.uk/pdbsum/3r4s PDBsum]</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=3r4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r4s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r4s RCSB], [http://www.ebi.ac.uk/pdbsum/3r4s PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BXC1_CLOBO BXC1_CLOBO]] Botulinum toxin acts by inhibiting neurotransmitter release. It binds to peripheral neuronal synapses, is internalized and moves by retrograde transport up the axon into the spinal cord where it can move between postsynaptic and presynaptic neurons. It inhibits neurotransmitter release by acting as a zinc endopeptidase that cleaves syntaxin.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 10:45, 19 December 2014

OCA — Fri, 19 Dec 2014 10:45:34 GMT

←Older revision		Revision as of 10:45, 19 December 2014
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-	~~{{STRUCTURE_3r4s\| PDB=3r4s \| SCENE= }}~~	+	==Cell entry of botulinum neurotoxin type C is dependent upon interaction with two ganglioside molecules==
-	===Cell entry of botulinum neurotoxin type C is dependent upon interaction with two ganglioside molecules===	+	<StructureSection load='3r4s' size='340' side='right' caption='[[3r4s]], [[Resolution\|resolution]] 2.15Å' scene=''>
-	~~{{ABSTRACT_PUBMED_21542861}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3r4s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R4S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R4S FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene>, <scene name='pdbligand=SLB:5-N-ACETYL-BETA-D-NEURAMINIC+ACID'>SLB</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3r4u\|3r4u]]</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=3r4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r4s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r4s RCSB], [http://www.ebi.ac.uk/pdbsum/3r4s PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The seven botulinum neurotoxins (BoNT) cause muscle paralysis by selectively cleaving core components of the vesicular fusion machinery. Their extraordinary activity primarily relies on highly specific entry into neurons. Data on BoNT/A, B, E, F and G suggest that entry follows a dual receptor interaction with complex gangliosides via an established ganglioside binding region and a synaptic vesicle protein. Here, we report high resolution crystal structures of the BoNT/C cell binding fragment alone and in complex with sialic acid. The WY-motif characteristic of the established ganglioside binding region was located on an exposed loop. Sialic acid was co-ordinated at a novel position neighbouring the binding pocket for synaptotagmin in BoNT/B and G and the sialic acid binding site in BoNT/D and TeNT respectively. Employing synaptosomes and immobilized gangliosides binding studies with BoNT/C mutants showed that the ganglioside binding WY-loop, the newly identified sialic acid-co-ordinating pocket and the area corresponding to the established ganglioside binding region of other BoNTs are involved in ganglioside interaction. Phrenic nerve hemidiaphragm activity tests employing ganglioside deficient mice furthermore evidenced that the biological activity of BoNT/C depends on ganglioside interaction with at least two binding sites. These data suggest a unique cell binding and entry mechanism for BoNT/C among clostridial neurotoxins.

-	~~==About this Structure==~~	+	The biological activity of botulinum neurotoxin type C is dependent upon novel types of ganglioside binding sites.,Strotmeier J, Gu S, Jutzi S, Mahrhold S, Zhou J, Pich A, Eichner T, Bigalke H, Rummel A, Jin R, Binz T Mol Microbiol. 2011 May 4. doi: 10.1111/j.1365-2958.2011.07682.x. PMID:21542861<ref>PMID:21542861</ref>
-	~~[[3r4s]]~~ is ~~a 2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Clostridium_botulinum Clostridium botulinum]~~. ~~Full crystallographic information is available from [http~~:/~~/oca~~.~~weizmann~~.ac.il/~~oca-bin/ocashort?id=3R4S OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:021542861</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Bontoxilysin]]		[[Category: Bontoxilysin]]
	[[Category: Clostridium botulinum]]		[[Category: Clostridium botulinum]]
-	[[Category: Bigalke, H.]]	+	[[Category: Bigalke, H]]
-	[[Category: Binz, T.]]	+	[[Category: Binz, T]]
-	[[Category: Gu, S.]]	+	[[Category: Gu, S]]
-	[[Category: Jin, R.]]	+	[[Category: Jin, R]]
-	[[Category: Jutzi, S.]]	+	[[Category: Jutzi, S]]
-	[[Category: Mahrhold, S.]]	+	[[Category: Mahrhold, S]]
-	[[Category: Pich, A.]]	+	[[Category: Pich, A]]
-	[[Category: Rummel, A.]]	+	[[Category: Rummel, A]]
-	[[Category: Strotmeier, J.]]	+	[[Category: Strotmeier, J]]
-	[[Category: Zhou, J.]]	+	[[Category: Zhou, J]]
	[[Category: Botulinum toxin]]		[[Category: Botulinum toxin]]
	[[Category: Ganglioside]]		[[Category: Ganglioside]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 07:49, 16 May 2013

OCA — Thu, 16 May 2013 07:49:10 GMT

←Older revision		Revision as of 07:49, 16 May 2013
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-	[[Image:3r4s.png\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3r4s", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3r4s\| PDB=3r4s \| SCENE= }}		{{STRUCTURE_3r4s\| PDB=3r4s \| SCENE= }}
-
	===Cell entry of botulinum neurotoxin type C is dependent upon interaction with two ganglioside molecules===		===Cell entry of botulinum neurotoxin type C is dependent upon interaction with two ganglioside molecules===
-
-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_21542861}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 21542861 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_21542861}}		{{ABSTRACT_PUBMED_21542861}}

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	==Reference==		==Reference==
-	<ref group="xtra">PMID:021542861</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021542861</ref><references group="xtra"/><references/>
	[[Category: Bontoxilysin]]		[[Category: Bontoxilysin]]
	[[Category: Clostridium botulinum]]		[[Category: Clostridium botulinum]]

OCA at 08:03, 13 July 2011

OCA — Wed, 13 Jul 2011 08:03:37 GMT

←Older revision		Revision as of 08:03, 13 July 2011
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-	[[Image:3r4s.~~jpg~~\|left\|200px]]	+	[[Image:3r4s.png\|left\|200px]]

	<!--		<!--
Line 35:		Line 35:
	[[Category: Strotmeier, J.]]		[[Category: Strotmeier, J.]]
	[[Category: Zhou, J.]]		[[Category: Zhou, J.]]
		+	[[Category: Botulinum toxin]]
		+	[[Category: Ganglioside]]
		+	[[Category: Hydrolase]]

OCA at 05:09, 8 June 2011

OCA — Wed, 08 Jun 2011 05:09:51 GMT

←Older revision		Revision as of 05:09, 8 June 2011
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-	~~'''Unreleased structure'''~~	+	[[Image:3r4s.jpg\|left\|200px]]

-	The ~~entry 3r4s~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3r4s", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3r4s\| PDB=3r4s \| SCENE= }}

-	~~Authors: Strotmeier, J., Gu, S., Jutzi, S., Mahrhold, S., Zhou, J., Pich, A., Bigalke, H., Rummel, A., Jin, R., Binz, T.~~	+	===Cell entry of botulinum neurotoxin type C is dependent upon interaction with two ganglioside molecules===

-	~~Description~~: ~~Cell entry of botulinum neurotoxin type C~~ is ~~dependent upon interaction~~ with ~~two ganglioside molecules~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21542861}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21542861 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21542861}}
		+
		+	==About this Structure==
		+	[[3r4s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R4S OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021542861</ref><references group="xtra"/>
		+	[[Category: Bontoxilysin]]
		+	[[Category: Clostridium botulinum]]
		+	[[Category: Bigalke, H.]]
		+	[[Category: Binz, T.]]
		+	[[Category: Gu, S.]]
		+	[[Category: Jin, R.]]
		+	[[Category: Jutzi, S.]]
		+	[[Category: Mahrhold, S.]]
		+	[[Category: Pich, A.]]
		+	[[Category: Rummel, A.]]
		+	[[Category: Strotmeier, J.]]
		+	[[Category: Zhou, J.]]

OCA at 05:19, 1 June 2011

OCA — Wed, 01 Jun 2011 05:19:29 GMT

←Older revision		Revision as of 05:19, 1 June 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3r4s is ON HOLD	+	The entry 3r4s is ON HOLD until Paper Publication

	Authors: Strotmeier, J., Gu, S., Jutzi, S., Mahrhold, S., Zhou, J., Pich, A., Bigalke, H., Rummel, A., Jin, R., Binz, T.		Authors: Strotmeier, J., Gu, S., Jutzi, S., Mahrhold, S., Zhou, J., Pich, A., Bigalke, H., Rummel, A., Jin, R., Binz, T.

	Description: Cell entry of botulinum neurotoxin type C is dependent upon interaction with two ganglioside molecules		Description: Cell entry of botulinum neurotoxin type C is dependent upon interaction with two ganglioside molecules