4j1l: Difference between revisions
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<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://www.rcsb.org/pdb/explore.do?structureId=4j1l RCSB], [http://www.ebi.ac.uk/pdbsum/4j1l 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=4j1l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j1l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j1l RCSB], [http://www.ebi.ac.uk/pdbsum/4j1l PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== 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. | |||
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== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Revision as of 22:29, 25 December 2014
Mutant Endotoxin TeNTMutant Endotoxin TeNT
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 PubMedBoNT/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 AlsoReferences
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