1hly

SOLUTION STRUCTURE OF HONGOTOXIN 1SOLUTION STRUCTURE OF HONGOTOXIN 1

Structural highlights 1hly is a 1 chain structure with sequence from Centruroides limbatus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 25 models Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KAX25_CENLM Potent selective inhibitor of Kv1.1/KCNA1, Kv1.2/KCNA2, Kv1.3/KCNA3 voltage-gated potassium channels. Weak inhibitor of Kv1.6/KCNA6 potassium channel. 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 Hongotoxin(1) (HgTX(1)), a 39-residue peptide recently isolated from the venom of Centruroides limbatus, blocks the voltage-gated K+ channels K(v)1.1, K(v)1.2, and K(v)1.3 at picomolar toxin concentrations (Koschak, A., Bugianesi, R. M., Mitterdorfer, J., Kaczorowski, G. J., Garcia, M. L., and Knaus, H. G. (1998) J. Biol. Chem. 273, 2639-2644). In this report, we determine the three-dimensional structure of HgTX(1) using NMR spectroscopy (PDB-code: 1HLY). HgTX(1) was found to possess a structure similar to previously characterized K+ channel toxins (e.g. margatoxin) consisting of a three-stranded antiparallel beta-sheet (residues 2-4, 26-30, and 33-37) and a helical conformation (part 3(10) helix and part alpha helix; residues 10-20). Due to the importance of residue Lys-28 for high-affinity interaction with the respective channels, lysine-reactive fluorescence dyes cannot be used to label wild-type HgTX(1). On the basis of previous studies (see above) and our NMR data, a HgTX(1) mutant (HgTX(1)-A19C) was engineered, expressed, and purified. HgTX(1)-A19C-SH was labeled using sulfhydryl-reactive Cy3-, Cy5-, and Alexa-dyes. Pharmacological characterization of fluorescently labeled HgTX(1)-A19C in radioligand binding studies indicated that these hongotoxin(1) analogues retain high-affinity for voltage-gated K+ channels and a respective pharmacological profile. Cy3- and Alexa-dye-labeled hongotoxin(1) analogues were used to investigate the localization of K+ channels in brain sections. The distribution of toxin binding closely follows the distribution of K(v)1.2 immunoreactivity with the highest expression levels in the cerebellar Purkinje cell layer. Taken together, these results demonstrate that fluorescently labeled HgTX(1) analogues comprise novel probes to characterize a subset of voltage-gated K+ channels. Synthesis, characterization, and application of cy-dye- and alexa-dye-labeled hongotoxin(1) analogues. The first high affinity fluorescence probes for voltage-gated K+ channels.,Pragl B, Koschak A, Trieb M, Obermair G, Kaufmann WA, Gerster U, Blanc E, Hahn C, Prinz H, Schutz G, Darbon H, Gruber HJ, Knaus HG Bioconjug Chem. 2002 May-Jun;13(3):416-25. PMID:12009929 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Potassium channel toxin 3D structures

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