1wpd

From Proteopedia

(Difference between revisions)

Revision as of 10:55, 10 September 2015

Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins

Structural highlights

1wpd is a 1 chain structure with sequence from Chactoid scorpion. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[KAX62_SCOMA] Blocks voltage-gated potassium channels (Shaker B, and Kv1.2/KCNA2 (IC(50)=0.8 nM)) and is also active on Kv1.1/KCNA1 (IC(50)=45 nM) Kv1.3/KCNA3 (IC(50)=180 nM). Also inhibits apamin-sensitive small conductance calcium-activated potassium (SK/KCNN) channels, and inhibits intermediate conductance calcium-activated potassium (KCa3.1/KCNN4) channels.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Maurotoxin (MTX) and HsTx1 are two scorpion toxins belonging to the alpha-KTx6 structural family. These 34-residue toxins, cross-linked by four disulfide bridges, share 59% sequence identity and fold along the classical alpha/beta scaffold. Despite these structural similarities, they fully differ in their pharmacological profiles. MTX is highly active on small (SK) and intermediate (IK) conductance Ca(2+)-activated (K(+)) channels and on voltage-gated Kv1.2 channel, whereas HsTx1 potently blocks voltage-gated Kv1.1 and Kv1.3 channels only. Here, we designed and chemically produced MTX-HsTx1, a chimera of both toxins that contains the N-terminal helical region of MTX (sequence 1-16) and the C-terminal beta-sheet region of HsTx1 (sequence 17-34). The three-dimensional structure of the peptide in solution was solved by (1)H NMR. MTX-HsTx1 displays the activity of MTX on SK channel, whereas it exhibits the pharmacological profile of HsTx1 on Kv1.1, Kv1.2, Kv1.3, and IK channels. These data demonstrate that the helical region of MTX exerts a key role in SK channel recognition, whereas the beta-sheet region of HsTx1 is crucial for activity on all other channel types tested.

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

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

References

↑ Avdonin V, Nolan B, Sabatier JM, De Waard M, Hoshi T. Mechanisms of maurotoxin action on Shaker potassium channels. Biophys J. 2000 Aug;79(2):776-87. PMID:10920011 doi:http://dx.doi.org/10.1016/S0006-3495(00)76335-1
↑ Castle NA, London DO, Creech C, Fajloun Z, Stocker JW, Sabatier JM. Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated potassium channels. Mol Pharmacol. 2003 Feb;63(2):409-18. PMID:12527813
↑ 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
↑ Kharrat R, Mabrouk K, Crest M, Darbon H, Oughideni R, Martin-Eauclaire MF, Jacquet G, el Ayeb M, Van Rietschoten J, Rochat H, Sabatier JM. Chemical synthesis and characterization of maurotoxin, a short scorpion toxin with four disulfide bridges that acts on K+ channels. Eur J Biochem. 1996 Dec 15;242(3):491-8. PMID:9022673
↑ Kharrat R, Mansuelle P, Sampieri F, Crest M, Oughideni R, Van Rietschoten J, Martin-Eauclaire MF, Rochat H, El Ayeb M. Maurotoxin, a four disulfide bridge toxin from Scorpio maurus venom: purification, structure and action on potassium channels. FEBS Lett. 1997 Apr 14;406(3):284-90. PMID:9136903
↑ 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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1wpd"

@@ Line 2: / Line 2: @@
 <StructureSection load='1wpd' size='340' side='right' caption='[[1wpd]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1wpd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Scorpio_maurus_palmatus Scorpio maurus palmatus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WPD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WPD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1wpd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Chactoid_scorpion Chactoid scorpion]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WPD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WPD 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=1wpd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wpd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1wpd RCSB], [http://www.ebi.ac.uk/pdbsum/1wpd PDBsum]</span></td></tr>
+</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=1wpd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wpd OCA], [http://pdbe.org/1wpd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wpd RCSB], [http://www.ebi.ac.uk/pdbsum/1wpd PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/KAX62_SCOMA KAX62_SCOMA]] Blocks voltage-gated potassium channels (Shaker B, and Kv1.2/KCNA2 (IC(50)=0.8 nM)) and is also active on Kv1.1/KCNA1 (IC(50)=45 nM) Kv1.3/KCNA3 (IC(50)=180 nM). Also inhibits apamin-sensitive small conductance calcium-activated potassium (SK/KCNN) channels, and inhibits intermediate conductance calcium-activated potassium (KCa3.1/KCNN4) channels.<ref>PMID:10920011</ref> <ref>PMID:12527813</ref> <ref>PMID:15498765</ref> <ref>PMID:9022673</ref> <ref>PMID:9136903</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 13: / Line 15: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1wpd" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 20: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Scorpio maurus palmatus]]
+[[Category: Chactoid scorpion]]
 [[Category: Andreotti, N]]
 [[Category: Beeton, C]]

1wpd

From Proteopedia

Revision as of 10:55, 10 September 2015

Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox