1wt7

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{{Seed}}
 
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[[Image:1wt7.png|left|200px]]
 
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==Solution structure of BuTX-MTX: a butantoxin-maurotoxin chimera==
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The line below this paragraph, containing "STRUCTURE_1wt7", creates the "Structure Box" on the page.
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<StructureSection load='1wt7' size='340' side='right'caption='[[1wt7]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1wt7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Tityus_serrulatus Tityus serrulatus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WT7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WT7 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 25 models</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1wt7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wt7 OCA], [https://pdbe.org/1wt7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wt7 RCSB], [https://www.ebi.ac.uk/pdbsum/1wt7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wt7 ProSAT]</span></td></tr>
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{{STRUCTURE_1wt7| PDB=1wt7 | SCENE= }}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/KA121_TITSE KA121_TITSE] Potently blocks Kv1.3/KCNA3, Kv1.2/KCNA2, and Shaker potassium channels (PubMed:24590385) and inhibits high conductance calcium-activated potassium channels (PubMed:10082164). The IC(50) of Kv1.3/KCNN3 and Kv1.2/KCNN2 are 0.55 nM and 6.19 nM respectively (PubMed:24590385). In addition, it stimulates the release of NO, IL-6 and TNF-alpha in J774.1 cells (PubMed:21549737) and presents a pro-inflammatory activity in mice (PubMed:23085190).<ref>PMID:10082164</ref> <ref>PMID:21549737</ref> <ref>PMID:23085190</ref> <ref>PMID:24590385</ref> [https://www.uniprot.org/uniprot/KAX62_SCOPA KAX62_SCOPA] Blocks voltage-gated potassium channels Kv1.2/KCNA2 (IC(50)=0.12-0.8 nM), KCa3.1/KCNN4 (IC(50)=1-2.2 nM), Shaker B (IC(50)=2.39-80 nM), Kv1.1/KCNA1 (IC(50)=37-45 or no activity, depending on the study), Kv1.3/KCNA3 (IC(50)=150-180 or no activity, depending on the study).<ref>PMID:10888198</ref> <ref>PMID:10920011</ref> <ref>PMID:12527813</ref> <ref>PMID:15498765</ref> <ref>PMID:18042681</ref> <ref>PMID:9022673</ref> <ref>PMID:9136903</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Scorpion toxins interact with their target ion channels through multiple molecular contacts. Because a "gain of function" approach has never been described to evaluate the importance of the molecular contacts in defining toxin affinity, we experimentally examined whether increasing the molecular contacts between a toxin and an ion channel directly impacts toxin affinity. For this purpose, we focused on two scorpion peptides, the well-characterized maurotoxin with its variant Pi1-like disulfide bridging (MTX(Pi1)), used as a molecular template, and butantoxin (BuTX), used as an N-terminal domain provider. BuTX is found to be 60-fold less potent than MTX(Pi1) in blocking Kv1.2 (IC(50) values of 165 nM for BuTX versus 2.8 nM for MTX(Pi1)). Removal of its N-terminal domain (nine residues) further decreases BuTX affinity for Kv1.2 by 5.6-fold, which is in agreement with docking simulation data showing the importance of this domain in BuTX-Kv1.2 interaction. Transfer of the BuTX N-terminal domain to MTX(Pi1) results in a chimera with five disulfide bridges (BuTX-MTX(Pi1)) that exhibits 22-fold greater affinity for Kv1.2 than MTX(Pi1) itself, in spite of the lower affinity of BuTX as compared to MTX(Pi1). Docking experiments performed with the 3-D structure of BuTX-MTX(Pi1) in solution, as solved by (1)H-NMR, reveal that the N-terminal domain of BuTX participates in the increased affinity for Kv1.2 through additional molecular contacts. Altogether, the data indicate that acting on molecular contacts between a toxin and a channel is an efficient strategy to modulate toxin affinity.
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===Solution structure of BuTX-MTX: a butantoxin-maurotoxin chimera===
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Increasing the molecular contacts between maurotoxin and Kv1.2 channel augments ligand affinity.,M'Barek S, Chagot B, Andreotti N, Visan V, Mansuelle P, Grissmer S, Marrakchi M, El Ayeb M, Sampieri F, Darbon H, Fajloun Z, De Waard M, Sabatier JM Proteins. 2005 Aug 15;60(3):401-11. PMID:15971207<ref>PMID:15971207</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1wt7" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_15971207}}, adds the Publication Abstract to the page
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*[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 15971207 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_15971207}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Large Structures]]
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1WT7 is a [[Single protein]] structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WT7 OCA].
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[[Category: Tityus serrulatus]]
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[[Category: Andreotti N]]
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==Reference==
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[[Category: Chagot B]]
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Increasing the molecular contacts between maurotoxin and Kv1.2 channel augments ligand affinity., M'Barek S, Chagot B, Andreotti N, Visan V, Mansuelle P, Grissmer S, Marrakchi M, El Ayeb M, Sampieri F, Darbon H, Fajloun Z, De Waard M, Sabatier JM, Proteins. 2005 Aug 15;60(3):401-11. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15971207 15971207]
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[[Category: Darbon H]]
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[[Category: Single protein]]
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[[Category: De Waard M]]
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[[Category: Andreotti, N.]]
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[[Category: El Ayeb M]]
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[[Category: Ayeb, M El.]]
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[[Category: Fajloun Z]]
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[[Category: Barek, S M.]]
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[[Category: Grissmer S]]
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[[Category: Chagot, B.]]
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[[Category: M'Barek S]]
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[[Category: Darbon, H.]]
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[[Category: Mansuelle P]]
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[[Category: Fajloun, Z.]]
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[[Category: Marrakchi M]]
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[[Category: Grissmer, S.]]
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[[Category: Sabatier J-M]]
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[[Category: Mansuelle, P.]]
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[[Category: Sampieri F]]
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[[Category: Marrakchi, M.]]
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[[Category: Visan V]]
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[[Category: Sabatier, J M.]]
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[[Category: Sampieri, F.]]
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[[Category: Visan, V.]]
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[[Category: Waard, M De.]]
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[[Category: Butantoxin]]
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[[Category: K+ channel]]
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[[Category: Maurotoxin]]
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[[Category: Molecular contact]]
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[[Category: Scorpion toxin]]
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[[Category: Toxin affinity]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:05:53 2008''
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Current revision

Solution structure of BuTX-MTX: a butantoxin-maurotoxin chimera

PDB ID 1wt7

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