5bqn
From Proteopedia
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/BXD_CLOBO BXD_CLOBO]] Botulinum 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 cleaves the '60-Lys-|-Leu-61' bond of synaptobrevins-1 and -2. | [[http://www.uniprot.org/uniprot/BXD_CLOBO BXD_CLOBO]] Botulinum 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 cleaves the '60-Lys-|-Leu-61' bond of synaptobrevins-1 and -2. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The botulinum neurotoxin type D is one of seven highly potent toxins produced by Clostridium botulinum which inhibit neurotransmission at cholinergic nerve terminals. A functional fragment derived from the toxin, LHn, consisting of the catalytic and translocation domains, has been heralded as a platform for the development of targeted secretion inhibitors. These secretion inhibitors are aimed at retargeting the toxin towards a specific cell type to inhibit vesicular secretion. Here we report crystal structures of LHn from serotype D at 2.3 A, and that of SXN101959 at 3.1 A resolution. SXN101959, a derivative that combines LHn from serotype D with a fragment of the growth hormone releasing hormone, has previously revealed promising results in inhibiting growth hormone release in pituitary somatotrophs. These structures offer for the first time insights into the translocation domain interaction with the catalytic domain in serotype D. Furthermore, structural information from small-angle X-ray scattering of LHn/D is compared among serotypes A, B, and D. Taken together, these results demonstrate the robustness of the 'LHn fold' across serotypes and its use in engineering additional polypeptide components with added functionality. Our study demonstrates the suitability of botulinum neurotoxin, and serotype D in particular, as a basis for engineering novel secretion inhibitors. | ||
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| + | Structural analysis of Clostridium botulinum neurotoxin type D as a platform for the development of targeted secretion inhibitors.,Masuyer G, Davies JR, Moore K, Chaddock JA, Ravi Acharya K Sci Rep. 2015 Sep 1;5:13397. doi: 10.1038/srep13397. PMID:26324071<ref>PMID:26324071</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 04:57, 9 September 2015
Crystal structure of the LHn fragment of botulinum neurotoxin type D, mutant H233Y E230Q
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