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| | ==Solution structure of alpha-KTx-6.21 (UroTx) from Urodacus yaschenkoi== | | ==Solution structure of alpha-KTx-6.21 (UroTx) from Urodacus yaschenkoi== |
| - | <StructureSection load='6mzt' size='340' side='right'caption='[[6mzt]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='6mzt' size='340' side='right'caption='[[6mzt]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6mzt]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MZT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MZT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6mzt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Urodacus_yaschenkoi Urodacus yaschenkoi]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MZT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MZT FirstGlance]. <br> |
| - | </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=6mzt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mzt OCA], [http://pdbe.org/6mzt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mzt RCSB], [http://www.ebi.ac.uk/pdbsum/6mzt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mzt ProSAT]</span></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=6mzt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mzt OCA], [https://pdbe.org/6mzt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mzt RCSB], [https://www.ebi.ac.uk/pdbsum/6mzt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mzt ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/KAX6L_UROYA KAX6L_UROYA] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6mzt" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6mzt" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Anangi, R]] | + | [[Category: Urodacus yaschenkoi]] |
| - | [[Category: Chin, Y K.Y]] | + | [[Category: Anangi R]] |
| - | [[Category: King, G F]] | + | [[Category: Chin YK-Y]] |
| - | [[Category: Luna-Ramirez, K]] | + | [[Category: King GF]] |
| - | [[Category: Cysteine-stabilized alpha-beta motif]]
| + | [[Category: Luna-Ramirez K]] |
| - | [[Category: Scopion toxin]]
| + | |
| - | [[Category: Toxin]]
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| Structural highlights
Function
KAX6L_UROYA
Publication Abstract from PubMed
Urotoxin (alpha-KTx 6), a peptide from venom of the Australian scorpion Urodacus yaschenkoi, is the most potent inhibitor of Kv1.2 described to date (IC50 = 160 pM). The native peptide also inhibits Kv1.1, Kv1.3 and KCa3.1 with nanomolar affinity but its low abundance in venom precluded further studies of its actions. Here we produced recombinant Urotoxin (rUro) and characterized the molecular determinants of Kv1 channel inhibition. The 3D structure of rUro determined using NMR spectroscopy revealed a canonical cysteine-stabilised alpha/beta (CSalpha/beta) fold. Functional assessment of rUro using patch-clamp electrophysiology revealed the importance of C-terminal amidation for potency against Kv1.1-1.3 and Kv1.5. Neutralization of the putative pore-blocking K25 residue in rUro by mutation to Ala resulted in a major decrease in rUro potency against all Kv channels tested, without perturbing the toxin's structure. Reciprocal mutations in the pore of Uro-sensitive Kv1.2 and Uro-resistant Kv1.5 channels revealed a direct interaction between Urotoxin and the Kv channel pore. Our experimental work supports postulating a mechanism of action in which occlusion of the permeation pathway by the K25 residue in Urotoxin is the basis of its Kv1 inhibitory activity. Docking analysis was consistent with occlusion of the pore by K25 and the requirement of a small, non-charged amino acid in the Kv1 channel vestibule to facilitate toxin-channel interactions. Finally, computational studies revealed key interactions between the amidated C-terminus of Urotoxin and a conserved Asp residue in the turret of Kv1 channels, offering a potential rationale for potency differences between native and recombinant Urotoxin.
Structural basis of the potency and selectivity of Urotoxin, a potent Kv1 blocker from scorpion venom.,Luna-Ramirez K, Csoti A, McArthur JR, Chin YKY, Anangi R, Najera RDC, Possani LD, King GF, Panyi G, Yu H, Adams DJ, Finol-Urdaneta RK Biochem Pharmacol. 2020 Apr;174:113782. doi: 10.1016/j.bcp.2019.113782. Epub 2019, Dec 25. PMID:31881193[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Luna-Ramirez K, Csoti A, McArthur JR, Chin YKY, Anangi R, Najera RDC, Possani LD, King GF, Panyi G, Yu H, Adams DJ, Finol-Urdaneta RK. Structural basis of the potency and selectivity of Urotoxin, a potent Kv1 blocker from scorpion venom. Biochem Pharmacol. 2020 Apr;174:113782. doi: 10.1016/j.bcp.2019.113782. Epub 2019, Dec 25. PMID:31881193 doi:http://dx.doi.org/10.1016/j.bcp.2019.113782
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