5vgv - Revision history

OCA at 13:48, 4 October 2023

2023-10-04T13:48:38Z

←Older revision		Revision as of 13:48, 4 October 2023
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	<StructureSection load='5vgv' size='340' side='right'caption='[[5vgv]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='5vgv' size='340' side='right'caption='[[5vgv]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vgv]] is a 1 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=5VGV OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5VGV FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vgv]] is a 1 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=5VGV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VGV FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</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]] 2.6Å</td></tr>
-	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Related_structure~~\|~~Related:]]</b></td><td class="sblockDat">[[5vgx\|5vgx~~]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</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])</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=5vgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vgv OCA], [https://pdbe.org/5vgv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vgv RCSB], [https://www.ebi.ac.uk/pdbsum/5vgv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vgv 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~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5vgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vgv OCA], [~~http~~://pdbe.org/5vgv PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5vgv RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5vgv PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5vgv ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~BXA1_CLOBO BXA1_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 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.	+	[https://www.uniprot.org/uniprot/BXA1_CLOBH BXA1_CLOBH] 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 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.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bacillus botulinus van ermengem 1896]]~~	+	[[Category: Clostridium botulinum]]
-	~~[[Category: Bontoxilysin~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Allen~~, K N~~]]	+	[[Category: Allen KN]]
-	[[Category: Carolan~~, J P]]~~	+	[[Category: Carolan JP]]
-	~~[[Category: Botulinum]]~~	+
-	~~[[Category: Metalloprotease]]~~	+
-	~~[[Category: Neurotoxin]]~~	+
-	~~[[Category: Toxin~~]]	+

OCA at 17:17, 11 December 2019

2019-12-11T17:17:45Z

←Older revision		Revision as of 17:17, 11 December 2019
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	==Structure of the C. botulinum neurotoxin serotype A with Cu bound==		==Structure of the C. botulinum neurotoxin serotype A with Cu bound==
-	<StructureSection load='5vgv' size='340' side='right' caption='[[5vgv]], [[Resolution\|resolution]] 2.60Å' scene=''>	+	<StructureSection load='5vgv' size='340' side='right'caption='[[5vgv]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vgv]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VGV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VGV FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vgv]] is a 1 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=5VGV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VGV FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5vgx\|5vgx]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5vgx\|5vgx]]</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])</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=5vgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vgv OCA], [http://pdbe.org/5vgv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vgv RCSB], [http://www.ebi.ac.uk/pdbsum/5vgv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vgv ProSAT]</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=5vgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vgv OCA], [http://pdbe.org/5vgv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vgv RCSB], [http://www.ebi.ac.uk/pdbsum/5vgv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vgv ProSAT]</span></td></tr>
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	</div>		</div>
	<div class="pdbe-citations 5vgv" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5vgv" 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: Large Structures]]
	[[Category: Allen, K N]]		[[Category: Allen, K N]]
	[[Category: Carolan, J P]]		[[Category: Carolan, J P]]

OCA at 08:23, 3 August 2017

2017-08-03T08:23:32Z

←Older revision		Revision as of 08:23, 3 August 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5vgv is ~~ON HOLD~~	+	==Structure of the C. botulinum neurotoxin serotype A with Cu bound==
		+	<StructureSection load='5vgv' size='340' side='right' caption='[[5vgv]], [[Resolution\|resolution]] 2.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5vgv]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VGV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VGV FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5vgx\|5vgx]]</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=5vgv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vgv OCA], [http://pdbe.org/5vgv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vgv RCSB], [http://www.ebi.ac.uk/pdbsum/5vgv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vgv ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BXA1_CLOBO BXA1_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 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.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Botulinum neurotoxin serotype A (BoNT/A) causes a debilitating and potentially fatal illness known as botulism. The toxin is also a bioterrorism threat, yet no pharmacological antagonist to counteract its effects has reached clinical approval. Existing strategies to negate BoNT/A intoxication have looked to antibodies, peptides, or organic small molecules as potential therapeutics. In this work, a departure from the traditional drug discovery mindset was pursued, in which the enzyme's susceptibility to metal ions was exploited. A screen of a series of metal salts showed marked inhibitory activity of group 11 and 12 metals against the BoNT/A light chain (LC) protease. Enzyme kinetics revealed that copper (I) and (II) cations displayed noncompetitive inhibition of the LC (Ki approximately 1 muM), while mercury (II) cations were 10-fold more potent. Crystallographic and mutagenesis studies elucidated a key binding interaction between Cys165 on BoNT/A LC and the inhibitory metals. As potential copper prodrugs, ligand-copper complexes were examined in a cell-based model and were found to prevent BoNT/A cleavage of the endogenous protein substrate, SNAP-25, even at low muM concentrations of complexes. Further investigation of the complexes suggested a bioreductive mechanism causing intracellular release of copper, which directly inhibited the BoNT/A protease. In vivo experiments demonstrated that copper (II) dithiocarbamate and bis(thiosemicarbazone) complexes could delay BoNT/A-mediated lethality in a rodent model, indicating their potential for treating the harmful effects of BoNT/A intoxication. Our studies illustrate that metals can be therapeutically viable enzyme inhibitors; moreover, enzymes that share homology with BoNT LCs may be similarly targeted with metals.

-	~~Authors~~:	+	Metal Ions Effectively Ablate the Action of Botulinum Neurotoxin A.,Bremer PT, Pellett S, Carolan JP, Tepp WH, Eubanks LM, Allen KN, Johnson EA, Janda KD J Am Chem Soc. 2017 May 31;139(21):7264-7272. doi: 10.1021/jacs.7b01084. Epub, 2017 May 19. PMID:28475321<ref>PMID:28475321</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5vgv" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Bontoxilysin]]
		+	[[Category: Allen, K N]]
		+	[[Category: Carolan, J P]]
		+	[[Category: Botulinum]]
		+	[[Category: Metalloprotease]]
		+	[[Category: Neurotoxin]]
		+	[[Category: Toxin]]

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

2017-04-19T11:26:01Z

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

←Older revision

Revision as of 11:26, 19 April 2017

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

2017-04-19T11:25:59Z

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

New page

'''Unreleased structure'''

The entry 5vgv is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]