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==Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by L-arginine hydroxamate== | ==Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by L-arginine hydroxamate== | ||
<StructureSection load='2imb' size='340' side='right' caption='[[2imb]], [[Resolution|resolution]] 2.41Å' scene=''> | <StructureSection load='2imb' size='340' side='right'caption='[[2imb]], [[Resolution|resolution]] 2.41Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2imb]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2imb]] 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=2IMB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IMB FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AHL:N-HYDROXY-L-ARGININAMIDE'>AHL</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=AHL:N-HYDROXY-L-ARGININAMIDE'>AHL</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]], [[2ima|2ima]], [[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]], [[2ima|2ima]], [[2imc|2imc]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">botA, atx, bna ([ | <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'>[ | <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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2imb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2imb OCA], [https://pdbe.org/2imb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2imb RCSB], [https://www.ebi.ac.uk/pdbsum/2imb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2imb ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
| Line 14: | Line 14: | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/im/2imb_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/im/2imb_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> | ||
| Line 31: | Line 31: | ||
==See Also== | ==See Also== | ||
*[[Botulinum neurotoxin|Botulinum neurotoxin]] | *[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 38: | Line 38: | ||
[[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]] | ||
Revision as of 14:18, 31 March 2021
Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by L-arginine hydroxamateClostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by L-arginine hydroxamate
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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