1bah

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

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

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OCA

[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

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