|
|
| (3 intermediate revisions by the same user not shown) |
| Line 1: |
Line 1: |
| | |
| ==Crystal Structure of BoNT/A LC complexed with Hydroxamate-based Inhibitor PT-1== | | ==Crystal Structure of BoNT/A LC complexed with Hydroxamate-based Inhibitor PT-1== |
| <StructureSection load='3qiy' size='340' side='right' caption='[[3qiy]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='3qiy' size='340' side='right'caption='[[3qiy]], [[Resolution|resolution]] 2.30Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3qiy]] is a 1 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=3QIY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QIY FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3qiy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum_A_str._Hall Clostridium botulinum A str. Hall]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QIY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QIY FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QI1:4-[BIS(4-CHLOROBENZYL)AMINO]-N-HYDROXYBUTANAMIDE'>QI1</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]] 2.3Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qix|3qix]], [[3qiz|3qiz]], [[3qj0|3qj0]]</td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=QI1:4-[BIS(4-CHLOROBENZYL)AMINO]-N-HYDROXYBUTANAMIDE'>QI1</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, CBO0806, CLC_0862, Neurotoxin Light Chain ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 Clostridium botulinum])</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=3qiy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qiy OCA], [https://pdbe.org/3qiy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qiy RCSB], [https://www.ebi.ac.uk/pdbsum/3qiy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qiy 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=3qiy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qiy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qiy RCSB], [http://www.ebi.ac.uk/pdbsum/3qiy PDBsum]</span></td></tr> | |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
| |
| == Publication Abstract from PubMed ==
| |
| Neurotoxins synthesized by Clostridium botulinum bacteria (BoNT), the etiological agent of human botulism, are extremely toxic proteins making them high-risk agents for bioterrorism. Small molecule inhibitor development has been focused on the light chain zinc-dependent metalloprotease domain of the neurotoxin, an effort that has been hampered by its relatively flexible active site. Developed in concert with structure-activity relationship studies, the X-ray crystal structures of the complex of BoNT serotype A light chain (BoNT/A LC) with three different micromolar potency hydroxamate-based inhibitors are reported here for the first time. Comparison with an unliganded BoNT/A LC structure reveals significant changes in the active site as a result of binding by the unique inhibitor scaffolds. The 60/70 loop at the opening of the active site pocket undergoes the largest conformational change, presumably through an induced-fit mechanism, resulting in the most compact catalytic pocket observed in all known BoNT/A LC structures.
| |
|
| |
| Structural Characterization of Three Novel Hydroxamate-based Zinc Chelating Inhibitors of the C. botulinum Serotype A Neurotoxin Light Chain Metalloprotease Reveals a Compact Binding Site Resulting from 60/70 Loop Flexibility.,Thompson AA, Jiao GS, Kim S, Thai A, Cregar-Hernandez L, Margosiak SA, Johnson AT, Han GW, O'Malley S, Stevens RC Biochemistry. 2011 Mar 24. PMID:21434688<ref>PMID:21434688</ref>
| |
|
| |
|
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| | ==See Also== |
| </div>
| | *[[Botulinum neurotoxin 3D structures|Botulinum neurotoxin 3D structures]] |
| == References == | |
| <references/>
| |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Bontoxilysin]] | | [[Category: Clostridium botulinum A str. Hall]] |
| [[Category: Clostridium botulinum]] | | [[Category: Large Structures]] |
| [[Category: Han, G W]] | | [[Category: Han GW]] |
| [[Category: Stevens, R C]] | | [[Category: Stevens RC]] |
| [[Category: Thompson, A A]] | | [[Category: Thompson AA]] |
| [[Category: Bont]]
| |
| [[Category: Botulinum]]
| |
| [[Category: Hydrolase-hydrolase inhibitor complex]]
| |
| [[Category: Hydroxamate]]
| |
| [[Category: Inhibitor]]
| |
| [[Category: Metalloprotease]]
| |
| [[Category: Neurotoxin]]
| |
| [[Category: Protease]]
| |
| [[Category: Toxin]]
| |
