2imc: Difference between revisions

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-[[Image:2imc.jpg|left|200px]]
- {{Structure
+==Clostridium botulinum Neurotoxin Serotype A Light Chain, Residues 1-424==
-|PDB= 2imc |SIZE=350|CAPTION= <scene name='initialview01'>2imc</scene>, resolution 2.00&Aring;
+<StructureSection load='2imc' size='340' side='right'caption='[[2imc]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
+<table><tr><td colspan='2'>[[2imc]] 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=2IMC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IMC FirstGlance]. <br>
-|ACTIVITY= <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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
-|GENE= botA, atx, bna ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 Clostridium botulinum])
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-|DOMAIN=
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2imc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2imc OCA], [https://pdbe.org/2imc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2imc RCSB], [https://www.ebi.ac.uk/pdbsum/2imc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2imc ProSAT]</span></td></tr>
-|RELATEDENTRY=[[2ilp|2ILP]], [[2ima|2IMA]], [[2imb|2IMB]]
+</table>
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2imc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2imc OCA], [http://www.ebi.ac.uk/pdbsum/2imc PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2imc RCSB]</span>
+== Function ==
-}}
+[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.
+== 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/2imc_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/main_output.php?pdb_ID=2imc ConSurf].
+<div style="clear:both"></div>
-'''Clostridium botulinum Neurotoxin Serotype A Light Chain, Residues 1-424'''
+==See Also==
+*[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]]
+__TOC__
-==Overview==
+</StructureSection>
-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.
-==About this Structure==
-IMC 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=2IMC OCA].
-==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]
-[[Category: Bontoxilysin]]
 [[Category: Clostridium botulinum]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Allen, K N.]]
+[[Category: Allen KN]]
-[[Category: Silvaggi, N R.]]
+[[Category: Silvaggi NR]]
-[[Category: clostridium botulinum neurotoxin serotype some]]
-[[Category: protease inhibitor]]
-[[Category: substrate specificity]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:46:12 2008''