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| | ==Mutant Endotoxin TeNT== | | ==Mutant Endotoxin TeNT== |
| - | <StructureSection load='4j1l' size='340' side='right' caption='[[4j1l]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='4j1l' size='340' side='right'caption='[[4j1l]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4j1l]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Clote Clote]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J1L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J1L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4j1l]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_tetani_E88 Clostridium tetani E88]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J1L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J1L FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">tetX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=212717 CLOTE])</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=4j1l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j1l OCA], [https://pdbe.org/4j1l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j1l RCSB], [https://www.ebi.ac.uk/pdbsum/4j1l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j1l 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/Tentoxilysin Tentoxilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.68 3.4.24.68] </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=4j1l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j1l OCA], [http://pdbe.org/4j1l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4j1l RCSB], [http://www.ebi.ac.uk/pdbsum/4j1l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4j1l ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TETX_CLOTE TETX_CLOTE]] Tetanus toxin acts by inhibiting neurotransmitter release. It binds to peripheral neuronal synapses, is internalized and moves by retrograde transport up the axon into the spinal cord where it can move between postsynaptic and presynaptic neurons. It inhibits neurotransmitter release by acting as a zinc endopeptidase that catalyzes the hydrolysis of the '76-Gln-|-Phe-77' bond of synaptobrevin-2. | + | [https://www.uniprot.org/uniprot/TETX_CLOTE TETX_CLOTE] Tetanus toxin acts by inhibiting neurotransmitter release. It binds to peripheral neuronal synapses, is internalized and moves by retrograde transport up the axon into the spinal cord where it can move between postsynaptic and presynaptic neurons. It inhibits neurotransmitter release by acting as a zinc endopeptidase that catalyzes the hydrolysis of the '76-Gln-|-Phe-77' bond of synaptobrevin-2. |
| | <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: Clote]] | + | [[Category: Clostridium tetani E88]] |
| - | [[Category: Tentoxilysin]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, S]] | + | [[Category: Chen S]] |
| - | [[Category: Guo, J]] | + | [[Category: Guo J]] |
| - | [[Category: Pan, X]] | + | [[Category: Pan X]] |
| - | [[Category: Zhao, Y]] | + | [[Category: Zhao Y]] |
| - | [[Category: Endotoxin]]
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| - | [[Category: Toxin]]
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| Structural highlights
Function
TETX_CLOTE Tetanus toxin acts by inhibiting neurotransmitter release. It binds to peripheral neuronal synapses, is internalized and moves by retrograde transport up the axon into the spinal cord where it can move between postsynaptic and presynaptic neurons. It inhibits neurotransmitter release by acting as a zinc endopeptidase that catalyzes the hydrolysis of the '76-Gln-|-Phe-77' bond of synaptobrevin-2.
Publication Abstract from PubMed
BoNT/B and TeNT cleave substrate VAMP2 at the same scissile bond, yet these two toxins showed different efficiency on substrate hydrolysis and had different requirements for the recognition of P2' site of VAMP2, E(78). These differences may be due to their different composition of their substrate recognition pockets in the active site. Swapping of LC/T S1' pocket residue, L(230), with the corresponding isoleucine in LC/B increased LC/T activity by approximately 25 fold, while swapping of LC/B S1' pocket residue, S(201), with the corresponding proline in LC/T increased LC/B activity by approximately 10 fold. Optimization of both S1 and S1' pocket residues of LC/T, LC/T (K(168)E, L(230)I) elevated LC/T activity by more than 100-fold. The highly active LC/T derivative engineered in this study has the potential to be used as a more effective tool to study mechanisms of exocytosis in central neuron. The LC/B derivative with elevated activity has the potential to be developed into novel therapy to minimize the impact of immunoresistance during BoNT/B therapy.
Engineering Clostridia Neurotoxins with elevated catalytic activity.,Guo J, Pan X, Zhao Y, Chen S Toxicon. 2013 Nov;74:158-66. doi: 10.1016/j.toxicon.2013.08.055. Epub 2013 Aug, 29. PMID:23994593[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Guo J, Pan X, Zhao Y, Chen S. Engineering Clostridia Neurotoxins with elevated catalytic activity. Toxicon. 2013 Nov;74:158-66. doi: 10.1016/j.toxicon.2013.08.055. Epub 2013 Aug, 29. PMID:23994593 doi:http://dx.doi.org/10.1016/j.toxicon.2013.08.055
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