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5k6d

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Structure of FS50 an antagonist of NaV1.5

Structural highlights

5k6d is a 2 chain structure with sequence from Xenopsylla cheopis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.139Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A2IAD2_9NEOP

Publication Abstract from PubMed

Naturally occurring toxins have been invaluable tools for the study of structural and functional relationships of voltage-gated sodium channels (VGSC). Few studies have been made of potential channel-modulating substances from blood-feeding arthropods. He we describe the characterization FS50, a salivary protein from the flea, Xenopsylla cheopis, that exhibits an inhibitory activity against the NaV1.5 channel with an IC50 of 1.58 muM. The pore-blocking mechanism of this toxin is evident from the kinetics of activation and inactivation suggesting that FS50 does not interfere with the voltage sensor of NaV1.5. FS50 exhibits high specificity for NaV1.5, since 10 muM FS50 had no discernable effect on voltage-gated Na+, K+ and Ca2+ channels in rat dorsal root ganglia or VGSC forms individually expressed in HEK 293T cells. Furthermore, intravenous injection of FS50 into rats and monkeys elicited recovery from arrhythmia induced by BaCl2, as would be expected from a blockade of NaV1.5. The crystal structure of FS50 revealed a betaalphabetabeta domain similar to that of scorpion beta toxin and a small N-terminal betaalphabeta domain. Site-directed mutagenesis experiments have implicated a basic surface including the side chains of Arg 6, His 11 and Lys 32 as potentially important in the FS50 NaV1.5 interaction.

Structure and Function of FS50, a salivary protein from the flea Xenopsylla cheopis that blocks the sodium channel NaV1.5.,Xu X, Zhang B, Yang S, An S, Ribeiro JM, Andersen JF Sci Rep. 2016 Nov 7;6:36574. doi: 10.1038/srep36574. PMID:27819327^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Xu X, Zhang B, Yang S, An S, Ribeiro JM, Andersen JF. Structure and Function of FS50, a salivary protein from the flea Xenopsylla cheopis that blocks the sodium channel NaV1.5. Sci Rep. 2016 Nov 7;6:36574. doi: 10.1038/srep36574. PMID:27819327 doi:http://dx.doi.org/10.1038/srep36574

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5k6d"

Categories: Large Structures | Xenopsylla cheopis | Andersen JF | Xu X

@@ Line 3: / Line 3: @@
 <StructureSection load='5k6d' size='340' side='right'caption='[[5k6d]], [[Resolution|resolution]] 1.14&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5k6d]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Xenopsylla_cheopis Xenopsylla cheopis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K6D OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5K6D FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5k6d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopsylla_cheopis Xenopsylla cheopis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K6D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K6D FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5k6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k6d OCA], [http://pdbe.org/5k6d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k6d RCSB], [http://www.ebi.ac.uk/pdbsum/5k6d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k6d ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.139&#8491;</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=5k6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k6d OCA], [https://pdbe.org/5k6d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k6d RCSB], [https://www.ebi.ac.uk/pdbsum/5k6d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k6d ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/A2IAD2_9NEOP A2IAD2_9NEOP]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 24: @@
 [[Category: Large Structures]]
 [[Category: Xenopsylla cheopis]]
-[[Category: Andersen, J F]]
+[[Category: Andersen JF]]
-[[Category: Xu, X]]
+[[Category: Xu X]]
-[[Category: Flea]]
-[[Category: Sodium channel]]
-[[Category: Unknown function]]
-[[Category: Xenopsylla]]

5k6d

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Current revision

Structure of FS50 an antagonist of NaV1.5

Structural highlights

Function

Publication Abstract from PubMed

References

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