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| ==Crystal structure of a three finger toxin== | | ==Crystal structure of a three finger toxin== |
| <StructureSection load='4rud' size='340' side='right'caption='[[4rud]], [[Resolution|resolution]] 1.95Å' scene=''> | | <StructureSection load='4rud' size='340' side='right'caption='[[4rud]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4rud]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RUD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RUD FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RUD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RUD FirstGlance]. <br> |
| </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> | | </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=4rud FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rud OCA], [https://pdbe.org/4rud PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rud RCSB], [https://www.ebi.ac.uk/pdbsum/4rud PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rud ProSAT]</span></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=4rud FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rud OCA], [https://pdbe.org/4rud PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rud RCSB], [https://www.ebi.ac.uk/pdbsum/4rud PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rud ProSAT]</span></td></tr> | |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| BACKGROUND AND PURPOSE: Animal toxins have contributed significantly to our understanding of the neurobiology of receptors and ion channels. We studied the venom of the coral snake Micrurus fulvius fulvius and identified and characterised the structure and pharmacology of a new homodimeric neurotoxin, fulditoxin, that exhibited novel pharmacology at nicotinic acetylcholine receptors (nAChRs). EXPERIMENTAL APPROACH: Fulditoxin was isolated by chromatography, chemically synthesised, its structure determined by X-ray crystallography, and its pharmacological actions on nAChRs characterised by organ bath assays and two-electrode voltage clamp electrophysiology. KEY RESULTS: Fulditoxin's distinct 1.95A quaternary structure revealed two short-chain three-finger alpha-neurotoxins (alpha-3FNTxs) non-covalently bound by hydrophobic interactions; and an ability to bind metal and form tetrameric complexes, not reported previously for three-finger proteins. Although fulditoxin lacked all conserved amino acids canonically important for inhibiting nAChRs, it produced postsynaptic neuromuscular blockade of chick muscle at nanomolar concentrations, comparable to the prototypical alpha-bungarotoxin. This neuromuscular blockade was completely reversible, which is unusual for snake alpha-3FNTxs. Fulditoxin, therefore, interacts with nAChRs by utilizing an alternate pharmacophore. Unlike short-chain alpha-3FNTxs that bind only to muscle nAChRs, fulditoxin utilises dimerization to expand its pharmacological targets to include human neuronal alpha4beta2, alpha7 and alpha3beta2 nAChRs which it blocked with IC50 values of 1.8, 7, and 12 muM, respectively. CONCLUSIONS AND IMPLICATIONS: Based on its distinct quaternary structure and unusual pharmacology, we named this new class of dimeric Micrurus neurotoxins represented by fulditoxin as Sigma-neurotoxins, which offers greater insight into understanding the interactions between nAChRs and peptide antagonists.
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| Fulditoxin, representing a new class of dimeric snake toxins, defines novel pharmacology at nicotinic acetylcholine receptors.,Foo CS, Jobichen C, Hassan-Puttaswamy V, Dekan Z, Tae HS, Bertrand D, Adams DJ, Alewood PF, Sivaraman J, Nirthanan S, Kini RM Br J Pharmacol. 2019 Dec 26. doi: 10.1111/bph.14954. PMID:31877243<ref>PMID:31877243</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 4rud" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Jobichen, C]] | | [[Category: Jobichen C]] |
| [[Category: Sivaraman, J]] | | [[Category: Sivaraman J]] |
| [[Category: Snake venom toxin]]
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| [[Category: Three finger toxin]]
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| [[Category: Toxin]]
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