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[[Image:1cmr.png|left|200px]]


{{STRUCTURE_1cmr| PDB=1cmr |  SCENE= }}
==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==
<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., &amp; 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.


===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===
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>


{{ABSTRACT_PUBMED_8679614}}
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1cmr" style="background-color:#fffaf0;"></div>


==About this Structure==
==See Also==
[[1cmr]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CMR OCA].
*[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:008679614</ref><references group="xtra"/>
__TOC__
[[Category: Drakopoulou, E.]]
</StructureSection>
[[Category: Gilquin, B.]]
[[Category: Large Structures]]
[[Category: Guenneugues, M.]]
[[Category: Leiurus hebraeus]]
[[Category: Menez, A.]]
[[Category: Drakopoulou E]]
[[Category: Vita, C.]]
[[Category: Gilquin B]]
[[Category: Zinn-Justin, S.]]
[[Category: Guenneugues M]]
[[Category: Antagonist of nicotinic acetylcholine receptor]]
[[Category: Menez A]]
[[Category: Curaremimetic protein]]
[[Category: Vita C]]
[[Category: Zinn-Justin S]]

Latest revision as of 02:52, 21 November 2024

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 STRUCTURESNMR 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

Structural highlights

1cmr is a 1 chain structure with sequence from Leiurus hebraeus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR, 18 models
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).[1] [2] [3] [4] [5] [6] [7]

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[8]

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

See Also

References

  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
  2. ↑ Yount NY, Yeaman MR. Multidimensional signatures in antimicrobial peptides. Proc Natl Acad Sci U S A. 2004 May 11;101(19):7363-8. Epub 2004 Apr 26. PMID:15118082 doi:10.1073/pnas.0401567101
  3. ↑ 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
  4. ↑ Lucchesi K, Ravindran A, Young H, Moczydlowski E. Analysis of the blocking activity of charybdotoxin homologs and iodinated derivatives against Ca2+-activated K+ channels. J Membr Biol. 1989 Aug;109(3):269-81. PMID:2477548 doi:10.1007/BF01870284
  5. ↑ Kasheverov IE, Oparin PB, Zhmak MN, Egorova NS, Ivanov IA, Gigolaev AM, Nekrasova OV, Serebryakova MV, Kudryavtsev DS, Prokopev NA, Hoang AN, Tsetlin VI, Vassilevski AA, Utkin YN. Scorpion toxins interact with nicotinic acetylcholine receptors. FEBS Lett. 2019 Oct;593(19):2779-2789. PMID:31276191 doi:10.1002/1873-3468.13530
  6. ↑ Grissmer S, Nguyen AN, Aiyar J, Hanson DC, Mather RJ, Gutman GA, Karmilowicz MJ, Auperin DD, Chandy KG. Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol Pharmacol. 1994 Jun;45(6):1227-34 PMID:7517498
  7. ↑ Garcia ML, Garcia-Calvo M, Hidalgo P, Lee A, MacKinnon R. Purification and characterization of three inhibitors of voltage-dependent K+ channels from Leiurus quinquestriatus var. hebraeus venom. Biochemistry. 1994 Jun 7;33(22):6834-9. PMID:8204618 doi:10.1021/bi00188a012
  8. ↑ Zinn-Justin S, Guenneugues M, Drakopoulou E, Gilquin B, Vita C, Menez A. 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. Biochemistry. 1996 Jul 2;35(26):8535-43. PMID:8679614 doi:10.1021/bi960466n
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