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2kir

From Proteopedia

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Current revision

Solution structure of a designer toxin, mokatoxin-1

Structural highlights

2kir is a 1 chain structure with sequence from Synthetic construct sequences. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Venomous animals immobilize prey using protein toxins that act on ion channels and other targets of biological importance. Broad use of toxins for biomedical research, diagnosis, and therapy has been limited by inadequate target discrimination, for example, among ion channel subtypes. Here, a synthetic toxin is produced by a new strategy to be specific for human Kv1.3 channels, critical regulators of immune T cells. A phage display library of 11,200 de novo proteins is designed using the alpha-KTx scaffold of 31 scorpion toxin sequences known or predicted to bind to potassium channels. Mokatoxin-1 (moka1) is isolated by affinity selection on purified target. Moka1 blocks Kv1.3 at nanomolar levels that do not inhibit Kv1.1, Kv1.2, or KCa1.1. As a result, moka1 suppresses CD3/28-induced cytokine secretion by T cells without cross-reactive gastrointestinal hyperactivity. The 3D structure of moka1 rationalizes its specificity and validates the engineering approach, revealing a unique interaction surface supported on an alpha-KTx scaffold. This scaffold-based/target-biased strategy overcomes many obstacles to production of selective toxins.

A designer ligand specific for Kv1.3 channels from a scorpion neurotoxin-based library.,Takacs Z, Toups M, Kollewe A, Johnson E, Cuello LG, Driessens G, Biancalana M, Koide A, Ponte CG, Perozo E, Gajewski TF, Suarez-Kurtz G, Koide S, Goldstein SA Proc Natl Acad Sci U S A. 2009 Dec 10. PMID:20007782^[1]

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

References

↑ Takacs Z, Toups M, Kollewe A, Johnson E, Cuello LG, Driessens G, Biancalana M, Koide A, Ponte CG, Perozo E, Gajewski TF, Suarez-Kurtz G, Koide S, Goldstein SA. A designer ligand specific for Kv1.3 channels from a scorpion neurotoxin-based library. Proc Natl Acad Sci U S A. 2009 Dec 10. PMID:20007782

1 Structural highlights
2 Evolutionary Conservation
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/2kir"

@@ Line 1: / Line 1: @@
 ==Solution structure of a designer toxin, mokatoxin-1==
-<StructureSection load='2kir' size='340' side='right' caption='[[2kir]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2kir' size='340' side='right'caption='[[2kir]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2kir]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KIR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KIR FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2kir]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KIR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KIR 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=2kir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kir OCA], [http://pdbe.org/2kir PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kir RCSB], [http://www.ebi.ac.uk/pdbsum/2kir PDBsum]</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=2kir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kir OCA], [https://pdbe.org/2kir PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kir RCSB], [https://www.ebi.ac.uk/pdbsum/2kir PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kir ProSAT]</span></td></tr>
 </table>
 == Evolutionary Conservation ==
@@ Line 9: / Line 10: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ki/2kir_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ki/2kir_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 28: / Line 29: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Synthetic construct sequences]]
 [[Category: Biancalana, M]]

2kir

From Proteopedia

Current revision

Solution structure of a designer toxin, mokatoxin-1

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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