2ima - Revision history

OCA at 09:03, 21 February 2024

2024-02-21T09:03:28Z

← Older revision		Revision as of 09:03, 21 February 2024
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	<StructureSection load='2ima' size='340' side='right'caption='[[2ima]], [[Resolution\|resolution]] 1.94Å' scene=''>		<StructureSection load='2ima' size='340' side='right'caption='[[2ima]], [[Resolution\|resolution]] 1.94Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2ima]] 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=2IMA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IMA FirstGlance]. <br>		<table><tr><td colspan='2'>[[2ima]] 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=2IMA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IMA FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=GB4:(2E)~~-~~3-(2,4-DICHLOROPHENYL)-N-HYDROXYACRYLAMIDE'>GB4</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]] 1.94Å</td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>~~[[~~Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto~~; ~~max-height: 3em;'>[[2ilp\|2ilp]], [[2imb\|2imb]], [[2imc\|2imc]]</div>~~</td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GB4:(2E)-3-(2,4-DICHLOROPHENYL)-N-HYDROXYACRYLAMIDE'>GB4</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 ([https://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~~'>~~[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=2ima FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ima OCA], [https://pdbe.org/2ima PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ima RCSB], [https://www.ebi.ac.uk/pdbsum/2ima PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ima 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=2ima FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ima OCA], [https://pdbe.org/2ima PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ima RCSB], [https://www.ebi.ac.uk/pdbsum/2ima PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ima ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[https://www.uniprot.org/uniprot/Q84GJ4_CLOBO Q84GJ4_CLOBO]
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ima ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ima ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	The potential for the use of Clostridial neurotoxins as bioweapons makes the development of small-molecule inhibitors of these deadly toxins a top priority. Recently, screening of a random hydroxamate library identified a small-molecule inhibitor of C. botulinum Neurotoxin Serotype A Light Chain (BoNT/A-LC), 4-chlorocinnamic hydroxamate, a derivative of which has been shown to have in vivo efficacy in mice and no toxicity. We describe the X-ray crystal structures of BoNT/A-LC in complexes with two potent small-molecule inhibitors. The structures of the enzyme with 4-chlorocinnamic hydroxamate or 2,4-dichlorocinnamic hydroxamate bound are compared to the structure of the enzyme complexed with L-arginine hydroxamate, an inhibitor with modest affinity. Taken together, this suite of structures provides surprising insights into the BoNT/A-LC active site, including unexpected conformational flexibility at the S1' site that changes the electrostatic environment of the binding pocket. Information gained from these structures will inform the design and optimization of more effective small-molecule inhibitors of BoNT/A-LC.

	Structures of Clostridium botulinum Neurotoxin Serotype A Light Chain complexed with small-molecule inhibitors highlight active-site flexibility.,Silvaggi NR, Boldt GE, Hixon MS, Kennedy JP, Tzipori S, Janda KD, Allen KN Chem Biol. 2007 May;14(5):533-42. PMID:17524984<ref>PMID:17524984</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 2ima" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
	*[[Botulinum neurotoxin 3D structures\|Botulinum neurotoxin 3D structures]]		*[[Botulinum neurotoxin 3D structures\|Botulinum neurotoxin 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__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: Clostridium botulinum neurotoxin serotype some]]~~
	~~[[Category: Hydrolase]]~~
	~~[[Category: Protease inhibitor]]~~
	~~[[Category: Substrate specificity]]~~
	~~[[Category: Substrate switching~~]]

OCA at 11:18, 31 March 2021

2021-03-31T11:18:40Z

← Older revision		Revision as of 11:18, 31 March 2021
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	==Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by 2,4-dichlorocinnamic hydroxamate==		==Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by 2,4-dichlorocinnamic hydroxamate==
	<StructureSection load='2ima' size='340' side='right' caption='[[2ima]], [[Resolution\|resolution]] 1.94Å' scene=''>		<StructureSection load='2ima' size='340' side='right'caption='[[2ima]], [[Resolution\|resolution]] 1.94Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2ima]] 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=2IMA OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2IMA FirstGlance]. <br>		<table><tr><td colspan='2'>[[2ima]] 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=2IMA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IMA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GB4:(2E)-3-(2,4-DICHLOROPHENYL)-N-HYDROXYACRYLAMIDE'>GB4</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" id="ligandDat"><scene name='pdbligand=GB4:(2E)-3-(2,4-DICHLOROPHENYL)-N-HYDROXYACRYLAMIDE'>GB4</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">[[2ilp\|2ilp]], [[2imb\|2imb]], [[2imc\|2imc]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ilp\|2ilp]], [[2imb\|2imb]], [[2imc\|2imc]]</div></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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">botA, atx, bna ([https://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'>[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=2ima FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ima OCA], [~~http~~://pdbe.org/2ima PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2ima RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2ima PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2ima 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=2ima FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ima OCA], [https://pdbe.org/2ima PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ima RCSB], [https://www.ebi.ac.uk/pdbsum/2ima PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ima ProSAT]</span></td></tr>
	</table>		</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
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	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/im/2ima_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/im/2ima_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
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	==See Also==		==See Also==
	*[[Botulinum neurotoxin\|Botulinum neurotoxin]]		*[[Botulinum neurotoxin 3D structures\|Botulinum neurotoxin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	[[Category: Bacillus botulinus van ermengem 1896]]		[[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 08:32, 18 October 2017

2017-10-18T08:32:03Z

← Older revision		Revision as of 08:32, 18 October 2017
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	==Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by 2,4-dichlorocinnamic hydroxamate==		==Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by 2,4-dichlorocinnamic hydroxamate==
	<StructureSection load='2ima' size='340' side='right' caption='[[2ima]], [[Resolution\|resolution]] 1.94Å' scene=''>		<StructureSection load='2ima' size='340' side='right' caption='[[2ima]], [[Resolution\|resolution]] 1.94Å' scene=''>
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	<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='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=2ima FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ima OCA], [http://pdbe.org/2ima PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ima RCSB], [http://www.ebi.ac.uk/pdbsum/2ima 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=2ima FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ima OCA], [http://pdbe.org/2ima PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ima RCSB], [http://www.ebi.ac.uk/pdbsum/2ima PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ima ProSAT]</span></td></tr>
	</table>		</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
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	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ima ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 15:01, 11 September 2015

2015-09-11T15:01:21Z

← Older revision		Revision as of 15:01, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='2ima' size='340' side='right' caption='[[2ima]], [[Resolution\|resolution]] 1.94Å' scene=''>		<StructureSection load='2ima' size='340' side='right' caption='[[2ima]], [[Resolution\|resolution]] 1.94Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2ima]] 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=2IMA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2IMA FirstGlance]. <br>		<table><tr><td colspan='2'>[[2ima]] 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=2IMA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2IMA FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GB4:(2E)-3-(2,4-DICHLOROPHENYL)-N-HYDROXYACRYLAMIDE'>GB4</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=GB4:(2E)-3-(2,4-DICHLOROPHENYL)-N-HYDROXYACRYLAMIDE'>GB4</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">[[2ilp\|2ilp]], [[2imb\|2imb]], [[2imc\|2imc]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ilp\|2ilp]], [[2imb\|2imb]], [[2imc\|2imc]]</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 ~~Clostridium botulinum~~])</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=2ima FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ima OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ima RCSB], [http://www.ebi.ac.uk/pdbsum/2ima 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=2ima FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ima OCA], [http://pdbe.org/2ima PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ima RCSB], [http://www.ebi.ac.uk/pdbsum/2ima PDBsum]</span></td></tr>
	</table>		</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
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	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 2ima" 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: Allen, K N]]		[[Category: Allen, K N]]
	[[Category: Silvaggi, N R]]		[[Category: Silvaggi, N R]]

OCA at 07:58, 16 January 2015

2015-01-16T07:58:57Z

← Older revision		Revision as of 07:58, 16 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2ima]] 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=2IMA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2IMA FirstGlance]. <br>		<table><tr><td colspan='2'>[[2ima]] 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=2IMA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2IMA FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GB4:(2E)-3-(2,4-DICHLOROPHENYL)-N-HYDROXYACRYLAMIDE'>GB4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GB4:(2E)-3-(2,4-DICHLOROPHENYL)-N-HYDROXYACRYLAMIDE'>GB4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ilp\|2ilp]], [[2imb\|2imb]], [[2imc\|2imc]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ilp\|2ilp]], [[2imb\|2imb]], [[2imc\|2imc]]</td></tr>
	<tr><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 Clostridium botulinum])</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 Clostridium botulinum])</td></tr>
	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ima FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ima OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ima RCSB], [http://www.ebi.ac.uk/pdbsum/2ima 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=2ima FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ima OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ima RCSB], [http://www.ebi.ac.uk/pdbsum/2ima PDBsum]</span></td></tr>
	<table>		</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 33:		Line 33:
	[[Category: Bontoxilysin]]		[[Category: Bontoxilysin]]
	[[Category: Clostridium botulinum]]		[[Category: Clostridium botulinum]]
	[[Category: Allen, K N.]]		[[Category: Allen, K N]]
	[[Category: Silvaggi, N R.]]		[[Category: Silvaggi, N R]]
	[[Category: Clostridium botulinum neurotoxin serotype some]]		[[Category: Clostridium botulinum neurotoxin serotype some]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 09:14, 30 September 2014

2014-09-30T09:14:09Z

← Older revision		Revision as of 09:14, 30 September 2014
Line 1:		Line 1:
	[[Image:~~2ima~~.~~png~~\|~~left~~\|~~200px~~]]		==Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by 2,4-dichlorocinnamic hydroxamate==
			<StructureSection load='2ima' size='340' side='right' caption='[[2ima]], [[Resolution\|resolution]] 1.94Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[2ima]] 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=2IMA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2IMA FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GB4:(2E)-3-(2,4-DICHLOROPHENYL)-N-HYDROXYACRYLAMIDE'>GB4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
			<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ilp\|2ilp]], [[2imb\|2imb]], [[2imc\|2imc]]</td></tr>
			<tr><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 Clostridium botulinum])</td></tr>
			<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ima FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ima OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ima RCSB], [http://www.ebi.ac.uk/pdbsum/2ima PDBsum]</span></td></tr>
			<table>
			== Evolutionary Conservation ==
			[[Image:Consurf_key_small.gif\|200px\|right]]
			Check<jmol>
			<jmolCheckbox>
			<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/im/2ima_consurf.spt"</scriptWhenChecked>
			<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
			<text>to colour the structure by Evolutionary Conservation</text>
			</jmolCheckbox>
			</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The potential for the use of Clostridial neurotoxins as bioweapons makes the development of small-molecule inhibitors of these deadly toxins a top priority. Recently, screening of a random hydroxamate library identified a small-molecule inhibitor of C. botulinum Neurotoxin Serotype A Light Chain (BoNT/A-LC), 4-chlorocinnamic hydroxamate, a derivative of which has been shown to have in vivo efficacy in mice and no toxicity. We describe the X-ray crystal structures of BoNT/A-LC in complexes with two potent small-molecule inhibitors. The structures of the enzyme with 4-chlorocinnamic hydroxamate or 2,4-dichlorocinnamic hydroxamate bound are compared to the structure of the enzyme complexed with L-arginine hydroxamate, an inhibitor with modest affinity. Taken together, this suite of structures provides surprising insights into the BoNT/A-LC active site, including unexpected conformational flexibility at the S1' site that changes the electrostatic environment of the binding pocket. Information gained from these structures will inform the design and optimization of more effective small-molecule inhibitors of BoNT/A-LC.

	~~{{STRUCTURE_2ima\| PDB=2ima \| SCENE= }}~~		Structures of Clostridium botulinum Neurotoxin Serotype A Light Chain complexed with small-molecule inhibitors highlight active-site flexibility.,Silvaggi NR, Boldt GE, Hixon MS, Kennedy JP, Tzipori S, Janda KD, Allen KN Chem Biol. 2007 May;14(5):533-42. PMID:17524984<ref>PMID:17524984</ref>

	~~===Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by 2~~,~~4-dichlorocinnamic hydroxamate===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~{{ABSTRACT_PUBMED_17524984}}~~		== References ==
			<references/>
	~~==About this Structure==~~		__TOC__
	~~[[2ima]] 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=2IMA OCA].~~		</StructureSection>

	==~~Reference~~==
	<~~ref group="xtra">PMID:017524984<~~/~~ref~~><~~references group="xtra"~~/>
	[[Category: Bontoxilysin]]		[[Category: Bontoxilysin]]
	[[Category: Clostridium botulinum]]		[[Category: Clostridium botulinum]]

OCA: Protected "2ima" [edit=sysop:move=sysop]

2013-01-07T14:09:13Z

Protected "2ima" [edit=sysop:move=sysop]

← Older revision	Revision as of 14:09, 7 January 2013
(No difference)

OCA at 14:09, 7 January 2013

2013-01-07T14:09:11Z

← Older revision		Revision as of 14:09, 7 January 2013
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	~~{{Seed}}~~
	[[Image:2ima.png\|left\|200px]]		[[Image:2ima.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_2ima", 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_2ima\| PDB=2ima \| SCENE= }}		{{STRUCTURE_2ima\| PDB=2ima \| SCENE= }}

	===Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by 2,4-dichlorocinnamic hydroxamate===		===Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by 2,4-dichlorocinnamic hydroxamate===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_17524984}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 17524984 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_17524984}}		{{ABSTRACT_PUBMED_17524984}}

	==About this Structure==		==About this Structure==
	~~2IMA~~ is a 2 ~~chains~~ structure ~~of sequences~~ 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=2IMA OCA].		[[2ima]] 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=2IMA OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~17524984~~</ref><references group="xtra"/>		<ref group="xtra">PMID:017524984</ref><references group="xtra"/>
	[[Category: Bontoxilysin]]		[[Category: Bontoxilysin]]
	[[Category: Clostridium botulinum]]		[[Category: Clostridium botulinum]]
Line 29:		Line 17:
	[[Category: Silvaggi, N R.]]		[[Category: Silvaggi, N R.]]
	[[Category: Clostridium botulinum neurotoxin serotype some]]		[[Category: Clostridium botulinum neurotoxin serotype some]]
			[[Category: Hydrolase]]
	[[Category: Protease inhibitor]]		[[Category: Protease inhibitor]]
	[[Category: Substrate specificity]]		[[Category: Substrate specificity]]
	[[Category: Substrate switching]]		[[Category: Substrate switching]]

	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 01:02:16 2009''~~

OCA at 23:02, 17 February 2009

2009-02-17T23:02:23Z

← Older revision		Revision as of 23:02, 17 February 2009
Line 20:		Line 20:

	==About this Structure==		==About this Structure==
	2IMA is a ~~[[Single protein]]~~ structure of ~~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=2IMA OCA].		2IMA is a 2 chains structure of sequences 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=2IMA OCA].

	==Reference==		==Reference==
	Structures of Clostridium botulinum Neurotoxin Serotype A Light Chain complexed with small-molecule inhibitors highlight active-site flexibility., Silvaggi NR, Boldt GE, Hixon MS, Kennedy JP, Tzipori S, Janda KD, Allen KN, Chem Biol. 2007 May;14(5):533-42. PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/17524984 17524984]~~		<ref group="xtra">PMID:17524984</ref><references group="xtra"/>
	[[Category: Bontoxilysin]]		[[Category: Bontoxilysin]]
	[[Category: Clostridium botulinum]]		[[Category: Clostridium botulinum]]
	~~[[Category: Single protein]]~~
	[[Category: Allen, K N.]]		[[Category: Allen, K N.]]
	[[Category: Silvaggi, N R.]]		[[Category: Silvaggi, N R.]]
Line 34:		Line 33:
	[[Category: Substrate switching]]		[[Category: Substrate switching]]

	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Tue Jul 29 08~~:29:~~12 2008~~''		''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 01:02:16 2009''

OCA at 05:29, 29 July 2008

2008-07-29T05:29:15Z

← Older revision		Revision as of 05:29, 29 July 2008
Line 1:		Line 1:
	[[Image:2ima.~~jpg~~\|left\|200px]]		{{Seed}}
			[[Image:2ima.png\|left\|200px]]

	<!--		<!--
Line 9:		Line 10:
	{{STRUCTURE_2ima\| PDB=2ima \| SCENE= }}		{{STRUCTURE_2ima\| PDB=2ima \| SCENE= }}

	~~'''~~Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by 2,4-dichlorocinnamic hydroxamate~~'''~~		===Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by 2,4-dichlorocinnamic hydroxamate===


	~~==Overview==~~		<!--
	The ~~potential for~~ the ~~use of Clostridial neurotoxins as bioweapons makes~~ the development of small-molecule inhibitors of these deadly toxins a top priority. Recently, screening of a random hydroxamate library identified a small-molecule inhibitor of C. botulinum Neurotoxin Serotype A Light Chain (~~BoNT~~/~~A-LC), 4-chlorocinnamic hydroxamate, a derivative of which has been shown to have in vivo efficacy in mice and no toxicity. We describe the X-ray crystal structures of BoNT~~/~~A-LC in complexes with two potent small-molecule inhibitors~~. The structures of the enzyme with 4-chlorocinnamic hydroxamate or 2,4-dichlorocinnamic hydroxamate bound are compared to the structure of the enzyme complexed with L-arginine hydroxamate, an inhibitor with modest affinity. ~~Taken together~~, ~~this suite of structures provides surprising insights into~~ the ~~BoNT/A-LC active site, including unexpected conformational flexibility at the S1' site that changes the electrostatic environment of the binding pocket~~. ~~Information gained from these structures will inform the design and optimization of more effective small~~-~~molecule inhibitors of BoNT/A~~-~~LC.~~		The line below this paragraph, {{ABSTRACT_PUBMED_17524984}}, adds the Publication Abstract to the page
			(as it appears on PubMed at http://www.pubmed.gov), where 17524984 is the PubMed ID number.
			-->
			{{ABSTRACT_PUBMED_17524984}}

	==About this Structure==		==About this Structure==
Line 29:		Line 33:
	[[Category: Substrate specificity]]		[[Category: Substrate specificity]]
	[[Category: Substrate switching]]		[[Category: Substrate switching]]
	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun May 4 07~~:38:52 2008''
			''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 08:29:12 2008''