5v8p - Revision history

OCA at 13:43, 4 October 2023

2023-10-04T13:43:52Z

←Older revision		Revision as of 13:43, 4 October 2023
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	<StructureSection load='5v8p' size='340' side='right'caption='[[5v8p]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='5v8p' size='340' side='right'caption='[[5v8p]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5v8p]] 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=5V8P OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5V8P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5v8p]] 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=5V8P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V8P FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=90G:N-[3-(4-chlorophenyl)-1H-pyrazol-5-yl]-2-sulfanylacetamide'>90G</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.501Å</td></tr>
-	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5v8u\|5v8u]]~~, [[~~5v8r~~\|~~5v8r~~]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=90G:N-[3-(4-chlorophenyl)-1H-pyrazol-5-yl]-2-sulfanylacetamide'>90G</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5v8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v8p OCA], [https://pdbe.org/5v8p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v8p RCSB], [https://www.ebi.ac.uk/pdbsum/5v8p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v8p 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=5v8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v8p OCA], [~~http~~://pdbe.org/5v8p PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5v8p RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5v8p PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5v8p 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: Silvaggi~~, N R]]~~	+	[[Category: Silvaggi NR]]
-	~~[[Category: Drug design]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Metalloprotease~~]]	+

OCA at 17:14, 11 December 2019

2019-12-11T17:14:33Z

←Older revision		Revision as of 17:14, 11 December 2019
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	==Small Molecule Inhibitor ABS-143 Bound to the Botulinum Neurotoxin Serotype A Light Chain==		==Small Molecule Inhibitor ABS-143 Bound to the Botulinum Neurotoxin Serotype A Light Chain==
-	<StructureSection load='5v8p' size='340' side='right' caption='[[5v8p]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='5v8p' size='340' side='right'caption='[[5v8p]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5v8p]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V8P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V8P FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5v8p]] 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=5V8P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V8P FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=90G:N-[3-(4-chlorophenyl)-1H-pyrazol-5-yl]-2-sulfanylacetamide'>90G</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=90G:N-[3-(4-chlorophenyl)-1H-pyrazol-5-yl]-2-sulfanylacetamide'>90G</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5v8u\|5v8u]], [[5v8r\|5v8r]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5v8u\|5v8u]], [[5v8r\|5v8r]]</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=5v8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v8p OCA], [http://pdbe.org/5v8p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v8p RCSB], [http://www.ebi.ac.uk/pdbsum/5v8p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v8p 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=5v8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v8p OCA], [http://pdbe.org/5v8p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v8p RCSB], [http://www.ebi.ac.uk/pdbsum/5v8p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v8p ProSAT]</span></td></tr>
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	</div>		</div>
	<div class="pdbe-citations 5v8p" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5v8p" 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: Silvaggi, N R]]		[[Category: Silvaggi, N R]]

OCA at 04:15, 4 August 2017

2017-08-04T04:15:44Z

←Older revision		Revision as of 04:15, 4 August 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5v8p is ~~ON HOLD until Paper~~ Publication	+	==Small Molecule Inhibitor ABS-143 Bound to the Botulinum Neurotoxin Serotype A Light Chain==
		+	<StructureSection load='5v8p' size='340' side='right' caption='[[5v8p]], [[Resolution\|resolution]] 2.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5v8p]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V8P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V8P FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=90G:N-[3-(4-chlorophenyl)-1H-pyrazol-5-yl]-2-sulfanylacetamide'>90G</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5v8u\|5v8u]], [[5v8r\|5v8r]]</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=5v8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v8p OCA], [http://pdbe.org/5v8p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v8p RCSB], [http://www.ebi.ac.uk/pdbsum/5v8p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v8p 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 neurotoxins (BoNTs) are the most toxic substances known to mankind and are the causative agents of the neuroparalytic disease botulism. Their ease of production and extreme toxicity have caused these neurotoxins to be classified as Tier 1 bioterrorist threat agents and have led to a sustained effort to develop countermeasures to treat intoxication in case of a bioterrorist attack. While timely administration of an approved antitoxin is effective in reducing the severity of botulism, reversing intoxication requires different strategies. In the present study, we evaluated ABS 252 and other mercaptoacetamide small molecule active-site inhibitors of BoNT/A light chain using an integrated multi-assay approach. ABS 252 showed inhibitory activity in enzymatic, cell-based and muscle activity assays, and importantly, produced a marked delay in time-to-death in mice. The results suggest that a multi-assay approach is an effective strategy for discovery of potential BoNT therapeutic candidates.

-	~~Authors: Allen~~, ~~K.N~~., Silvaggi, N.R.	+	Small molecule metalloprotease inhibitor with in vitro, ex vivo and in vivo efficacy against botulinum neurotoxin serotype A.,Jacobson AR, Adler M, Silvaggi NR, Allen KN, Smith GM, Fredenburg RA, Stein RL, Park JB, Feng X, Shoemaker CB, Deshpande SS, Goodnough MC, Malizio CJ, Johnson EA, Pellett S, Tepp WH, Tzipori S Toxicon. 2017 Jul 8;137:36-47. doi: 10.1016/j.toxicon.2017.06.016. PMID:28698055<ref>PMID:28698055</ref>

-	~~Description: Small Molecule Inhibitor ABS-143 Bound to~~ the ~~Botulinum Neurotoxin Serotype A Light Chain~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Silvaggi~~, N.R]]	+	<div class="pdbe-citations 5v8p" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Allen~~, K.N]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Bontoxilysin]]
		+	[[Category: Allen, K N]]
		+	[[Category: Silvaggi, N R]]
		+	[[Category: Drug design]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Metalloprotease]]

OCA at 12:04, 27 April 2017

2017-04-27T12:04:52Z

←Older revision		Revision as of 12:04, 27 April 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5v8p is ON HOLD	+	The entry 5v8p is ON HOLD until Paper Publication

	Authors: Allen, K.N., Silvaggi, N.R.		Authors: Allen, K.N., Silvaggi, N.R.

OCA: Protected "5v8p" [edit=sysop:move=sysop]

2017-04-05T11:45:07Z

Protected "5v8p" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:45, 5 April 2017

OCA: New page: '''Unreleased structure''' The entry 5v8p is ON HOLD Authors: Allen, K.N., Silvaggi, N.R. Description: Small Molecule Inhibitor ABS-143 Bound to the Botulinum Neurotoxin Serotype A Lig...

2017-04-05T11:45:05Z

New page: '''Unreleased structure''' The entry 5v8p is ON HOLD Authors: Allen, K.N., Silvaggi, N.R. Description: Small Molecule Inhibitor ABS-143 Bound to the Botulinum Neurotoxin Serotype A Lig...

New page

'''Unreleased structure'''

The entry 5v8p is ON HOLD

Authors: Allen, K.N., Silvaggi, N.R.

Description: Small Molecule Inhibitor ABS-143 Bound to the Botulinum Neurotoxin Serotype A Light Chain
[[Category: Unreleased Structures]]
[[Category: Silvaggi, N.R]]
[[Category: Allen, K.N]]