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New page: left|200px<br /><applet load="1cmr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cmr" /> '''NMR SOLUTION STRUCTURE OF A CHIMERIC PROTEIN... |
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== | ==NMR SOLUTION STRUCTURE OF A CHIMERIC PROTEIN, DESIGNED BY TRANSFERRING A FUNCTIONAL SNAKE BETA-HAIRPIN INTO A SCORPION ALPHA/BETA SCAFFOLD (PH 3.5, 20C), NMR, 18 STRUCTURES== | ||
The alpha/beta scorpion fold is shared by scorpion toxins, insect | <StructureSection load='1cmr' size='340' side='right'caption='[[1cmr]]' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1cmr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leiurus_hebraeus Leiurus hebraeus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CMR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CMR FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 18 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=1cmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cmr OCA], [https://pdbe.org/1cmr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cmr RCSB], [https://www.ebi.ac.uk/pdbsum/1cmr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cmr ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/KAX11_LEIHE KAX11_LEIHE] This toxin inhibits numerous potassium channels: shaker (Ki=227 nM), Kv1.2/KCNA2 (nanomolar range), Kv1.3/KCNA3 (nanomolar range), Kv1.5/KCNA5 (Kd>100 nM), Kv1.6/KCNA6 (Ki=22 nM), KCa1.1/KCNMA1 (IC(50)=5.9 nM). It blocks channel activity by a simple bimolecular inhibition process. It also shows a weak interaction with nicotinic acetylcholine receptors (nAChR), suggesting it may weakly inhibit it (PubMed:31276191). It also exhibits pH-specific antimicrobial activities against bacteria (B.subtilis, E.coli and S.aureus) and the fungus C.albicans (PubMed:15118082).<ref>PMID:12527813</ref> <ref>PMID:15118082</ref> <ref>PMID:20007782</ref> <ref>PMID:2477548</ref> <ref>PMID:31276191</ref> <ref>PMID:7517498</ref> <ref>PMID:8204618</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The alpha/beta scorpion fold is shared by scorpion toxins, insect defensins, and plant thionins. This small and functionally versatile template contains an alpha-helix and a triple beta-sheet linked by three disulfide bridges. With the view to introduce novel functional centers within this fold, we replaced the sequence (the cysteines and glycines excepted) of the original beta-hairpin of a scorpion toxin by the sequence of a beta-hairpin that forms part of the site by which snake neurotoxins bind to nicotinic acetylcholine receptors (AcChOR). The resulting chimeric protein, synthesized by chemical means, binds to AcChOR, though with a lower affinity than the snake toxins [Drakopoulou; E., Zinn-Justin, S., Guenneugues, M., Gilquin, B., Menez, A., & Vita, C. (1996) J. Biol. Chem. 271, 11979-11987]. The work described in this paper is an attempt to clarify the structural consequences associated with the transfer of the beta-hairpin. We report the determination of the three-dimensional solution structure of the chimeric protein by proton NMR spectroscopy and molecular dynamics calculations. Comparison of the structure of the chimera with those of the scorpion alpha/beta toxin and of the snake neurotoxin shows that (i) the new protein folds as an alpha/beta motif and (ii) the beta-hairpins of the chimera and of the curaremimetic toxin adopt a similar conformation. A closer inspection of the differences between the structures of the original and transferred beta-hairpins allows rationalization of the biological properties of the chimera. | |||
Transfer of a beta-hairpin from the functional site of snake curaremimetic toxins to the alpha/beta scaffold of scorpion toxins: three-dimensional solution structure of the chimeric protein.,Zinn-Justin S, Guenneugues M, Drakopoulou E, Gilquin B, Vita C, Menez A Biochemistry. 1996 Jul 2;35(26):8535-43. PMID:8679614<ref>PMID:8679614</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1cmr" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Leiurus hebraeus]] | |||
[[Category: Drakopoulou E]] | |||
[[Category: Gilquin B]] | |||
[[Category: Guenneugues M]] | |||
[[Category: Menez A]] | |||
[[Category: Vita C]] | |||
[[Category: Zinn-Justin S]] | |||
