1bah

From Proteopedia

(Difference between revisions)

Current revision

A TWO DISULFIDE DERIVATIVE OF CHARYBDOTOXIN WITH DISULFIDE 13-33 REPLACED BY TWO ALPHA-AMINOBUTYRIC ACIDS, NMR, 30 STRUCTURES

Structural highlights

1bah is a 1 chain structure with sequence from Leiurus quinquestriatus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 30 models
Ligands:	,
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]

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

The alpha/beta scorpion fold consisting of a short alpha-helix and beta-sheet is a structural motif common to scorpion toxins, insect defensins, and plant gamma-thionins that invariably contains three disulfides. CHABII is a two-disulfide derivative of the scorpion toxin charybdotoxin (ChTX), chemically synthesized by inserting two L-alpha-aminobutyric acids in place of the two half-cystine residues involved in the disulfide 13-33. This disulfide is one of the two disulfides which connect the alpha-helix to the beta-sheet. The solution structure of CHABII was determined at pH 6.3 and 5 degrees C using 2D NMR and simulated annealing from 513 distance and 46 dihedral angle constraints. The NMR structure of CHABII is well-defined as judged from the low value of the averaged backbone rms deviation between the 30 lowest energy structures and the energy-minimized mean structure ((rmsd) = 0.65 A for the entire sequence and 0.48 A for the segment 3-36). Analysis and comparison of the solution structures of CHABII and ChTX lead to the following conclusions: (i) the fold of CHABII is similar to that of ChTX as indicated by the low value of the averaged backbone atomic rms deviation between the 10 lowest energy solution structures of the two proteins (1.44 A); (ii) the packing of the hydrophobic core is well-preserved, underlying the critical structural role of the hydrophobic interactions even for such a small and cysteine-rich protein as ChTX.

NMR solution structure of a two-disulfide derivative of charybdotoxin: structural evidence for conservation of scorpion toxin alpha/beta motif and its hydrophobic side chain packing.,Song J, Gilquin B, Jamin N, Drakopoulou E, Guenneugues M, Dauplais M, Vita C, Menez A Biochemistry. 1997 Apr 1;36(13):3760-6. PMID:9092804^[8]

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

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Song J, Gilquin B, Jamin N, Drakopoulou E, Guenneugues M, Dauplais M, Vita C, Menez A. NMR solution structure of a two-disulfide derivative of charybdotoxin: structural evidence for conservation of scorpion toxin alpha/beta motif and its hydrophobic side chain packing. Biochemistry. 1997 Apr 1;36(13):3760-6. PMID:9092804 doi:http://dx.doi.org/10.1021/bi962720h

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==A TWO DISULFIDE DERIVATIVE OF CHARYBDOTOXIN WITH DISULFIDE 13-33 REPLACED BY TWO ALPHA-AMINOBUTYRIC ACIDS, NMR, 30 STRUCTURES==
-<StructureSection load='1bah' size='340' side='right' caption='[[1bah]], [[NMR_Ensembles_of_Models | 30 NMR models]]' scene=''>
+<StructureSection load='1bah' size='340' side='right'caption='[[1bah]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1bah]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Egyptian_scorpion Egyptian scorpion]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BAH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BAH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1bah]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leiurus_quinquestriatus Leiurus quinquestriatus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BAH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BAH FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 30 models</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=1bah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bah OCA], [http://pdbe.org/1bah PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1bah RCSB], [http://www.ebi.ac.uk/pdbsum/1bah PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1bah ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></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=1bah FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bah OCA], [https://pdbe.org/1bah PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bah RCSB], [https://www.ebi.ac.uk/pdbsum/1bah PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bah ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/KAX11_LEIQH KAX11_LEIQH]] Potent selective inhibitor of high conductance (maxi-K), different medium and small conductance calcium-activated potassium channels (KCa/KCNM), as well as a voltage-dependent potassium channel (Kv1.3/KCNA3). It appears to block channel activity by a simple bimolecular inhibition process.<ref>PMID:15118082</ref>   Has a pH-specific antimicrobial activity against bacteria (B.subtilis, E.coli and S.aureus) and the fungus C.albicans.<ref>PMID:15118082</ref>
+[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ba/1bah_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ba/1bah_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 30: / Line 31: @@
 ==See Also==
-*[[NMR Ensembles of Models|NMR Ensembles of Models]]
+*[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]]
-*[[User:Eric Martz/Entertaining PDB codes|User:Eric Martz/Entertaining PDB codes]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Egyptian scorpion]]
+[[Category: Large Structures]]
-[[Category: Dauplais, M]]
+[[Category: Leiurus quinquestriatus]]
-[[Category: Gilquin, B]]
+[[Category: Dauplais M]]
-[[Category: Guenneugues, M]]
+[[Category: Gilquin B]]
-[[Category: Jamin, N]]
+[[Category: Guenneugues M]]
-[[Category: Menez, A]]
+[[Category: Jamin N]]
-[[Category: Song, J]]
+[[Category: Menez A]]
-[[Category: Vita, C]]
+[[Category: Song J]]
-[[Category: Charybdotoxin]]
+[[Category: Vita C]]
-[[Category: Neurotoxin]]
-[[Category: Potassium channel inhibitor]]
-[[Category: Toxin]]

1bah

From Proteopedia

Current revision

A TWO DISULFIDE DERIVATIVE OF CHARYBDOTOXIN WITH DISULFIDE 13-33 REPLACED BY TWO ALPHA-AMINOBUTYRIC ACIDS, NMR, 30 STRUCTURES

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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