1y2p: Difference between revisions

Latest revision as of 07:43, 23 October 2024

Solution structure of Hstx3P

Structural highlights

1y2p is a 1 chain structure with sequence from Heterometrus spinifer. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 20 models
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KAX63_HETSP Potently blocks voltage-gated potassium channels Kv1.1/KCNA1 and Kv1.3/KCNA3. Mildly blocks intermediate (IK) conductance calcium-activated potassium channels (KCa3.1/KCNN4) and ERG1/Kv11.1/KCNH2.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Animal toxins are highly reticulated and structured polypeptides that adopt a limited number of folds. In scorpion species, the most represented fold is the alpha/beta scaffold in which an helical structure is connected to an antiparallel beta-sheet by two disulfide bridges. The intimate relationship existing between peptide reticulation and folding remains poorly understood. Here, we investigated the role of disulfide bridging on the 3D structure of HsTx1, a scorpion toxin potently active on Kv1.1 and Kv1.3 channels. This toxin folds along the classical alpha/beta scaffold but belongs to a unique family of short-chain, four disulfide-bridged toxins. Removal of the fourth disulfide bridge of HsTx1 does not affect its helical structure, whereas its two-stranded beta-sheet is altered from a twisted to a nontwisted configuration. This structural change in HsTx1 is accompanied by a marked decrease in Kv1.1 and Kv1.3 current blockage, and by alterations in the toxin to channel molecular contacts. In contrast, a similar removal of the fourth disulfide bridge of Pi1, another scorpion toxin from the same structural family, has no impact on its 3D structure, pharmacology, or channel interaction. These data highlight the importance of disulfide bridging in reaching the correct bioactive conformation of some toxins.

The impact of the fourth disulfide bridge in scorpion toxins of the alpha-KTx6 subfamily.,Carrega L, Mosbah A, Ferrat G, Beeton C, Andreotti N, Mansuelle P, Darbon H, De Waard M, Sabatier JM Proteins. 2005 Dec 1;61(4):1010-23. PMID:16247791^[4]

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

References

↑ Regaya I, Beeton C, Ferrat G, Andreotti N, Darbon H, De Waard M, Sabatier JM. Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins. J Biol Chem. 2004 Dec 31;279(53):55690-6. Epub 2004 Oct 21. PMID:15498765 doi:M410055200
↑ Abdel-Mottaleb Y, Corzo G, Martin-Eauclaire MF, Satake H, Ceard B, Peigneur S, Nambaru P, Bougis PE, Possani LD, Tytgat J. A common "hot spot" confers hERG blockade activity to alpha-scorpion toxins affecting K+ channels. Biochem Pharmacol. 2008 Sep 15;76(6):805-15. doi: 10.1016/j.bcp.2008.07.008. Epub, 2008 Jul 18. PMID:18687312 doi:https://dx.doi.org/10.1016/j.bcp.2008.07.008
↑ Lebrun B, Romi-Lebrun R, Martin-Eauclaire MF, Yasuda A, Ishiguro M, Oyama Y, Pongs O, Nakajima T. A four-disulphide-bridged toxin, with high affinity towards voltage-gated K+ channels, isolated from Heterometrus spinnifer (Scorpionidae) venom. Biochem J. 1997 Nov 15;328 ( Pt 1):321-7. PMID:9359871
↑ Carrega L, Mosbah A, Ferrat G, Beeton C, Andreotti N, Mansuelle P, Darbon H, De Waard M, Sabatier JM. The impact of the fourth disulfide bridge in scorpion toxins of the alpha-KTx6 subfamily. Proteins. 2005 Dec 1;61(4):1010-23. PMID:16247791 doi:10.1002/prot.20681

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Regaya I, Beeton C, Ferrat G, Andreotti N, Darbon H, De Waard M, Sabatier JM. Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins. J Biol Chem. 2004 Dec 31;279(53):55690-6. Epub 2004 Oct 21. PMID:15498765 doi:M410055200

[2] Abdel-Mottaleb Y, Corzo G, Martin-Eauclaire MF, Satake H, Ceard B, Peigneur S, Nambaru P, Bougis PE, Possani LD, Tytgat J. A common "hot spot" confers hERG blockade activity to alpha-scorpion toxins affecting K+ channels. Biochem Pharmacol. 2008 Sep 15;76(6):805-15. doi: 10.1016/j.bcp.2008.07.008. Epub, 2008 Jul 18. PMID:18687312 doi:https://dx.doi.org/10.1016/j.bcp.2008.07.008

[3] Lebrun B, Romi-Lebrun R, Martin-Eauclaire MF, Yasuda A, Ishiguro M, Oyama Y, Pongs O, Nakajima T. A four-disulphide-bridged toxin, with high affinity towards voltage-gated K+ channels, isolated from Heterometrus spinnifer (Scorpionidae) venom. Biochem J. 1997 Nov 15;328 ( Pt 1):321-7. PMID:9359871

[4] Carrega L, Mosbah A, Ferrat G, Beeton C, Andreotti N, Mansuelle P, Darbon H, De Waard M, Sabatier JM. The impact of the fourth disulfide bridge in scorpion toxins of the alpha-KTx6 subfamily. Proteins. 2005 Dec 1;61(4):1010-23. PMID:16247791 doi:10.1002/prot.20681

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[4]

@@ Line 1: / Line 1: @@
 ==Solution structure of Hstx3P==
-<StructureSection load='1y2p' size='340' side='right'caption='[[1y2p]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='1y2p' size='340' side='right'caption='[[1y2p]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1y2p]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y2P FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1y2p]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Heterometrus_spinifer Heterometrus spinifer]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y2P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y2P FirstGlance]. <br>
-</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=1y2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y2p OCA], [https://pdbe.org/1y2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y2p RCSB], [https://www.ebi.ac.uk/pdbsum/1y2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y2p ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=1y2p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y2p OCA], [https://pdbe.org/1y2p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y2p RCSB], [https://www.ebi.ac.uk/pdbsum/1y2p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y2p ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/KAX63_HETSP KAX63_HETSP]] Potently blocks voltage-gated potassium channels Kv1.1/KCNA1 and Kv1.3/KCNA3. Mildly blocks intermediate (IK) conductance calcium-activated potassium channels (KCa3.1/KCNN4) and ERG1/Kv11.1/KCNH2.<ref>PMID:15498765</ref> <ref>PMID:18687312</ref> <ref>PMID:9359871</ref>
+[https://www.uniprot.org/uniprot/KAX63_HETSP KAX63_HETSP] Potently blocks voltage-gated potassium channels Kv1.1/KCNA1 and Kv1.3/KCNA3. Mildly blocks intermediate (IK) conductance calcium-activated potassium channels (KCa3.1/KCNN4) and ERG1/Kv11.1/KCNH2.<ref>PMID:15498765</ref> <ref>PMID:18687312</ref> <ref>PMID:9359871</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Heterometrus spinifer]]
 [[Category: Large Structures]]
-[[Category: Darbon, H]]
+[[Category: Darbon H]]
-[[Category: Gariga, L]]
+[[Category: Gariga L]]
-[[Category: Mosbah, A]]
+[[Category: Mosbah A]]
-[[Category: Sabatier, J M]]
+[[Category: Sabatier JM]]
-[[Category: Hstx3p]]
-[[Category: Potassium channel]]
-[[Category: Toxin]]

1y2p: Difference between revisions

Latest revision as of 07:43, 23 October 2024

Solution structure of Hstx3P

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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