1hly
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1hly.jpg|left|200px]] | [[Image:1hly.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1hly", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | | | + | or leave the SCENE parameter empty for the default display. |
| - | | | + | --> |
| - | + | {{STRUCTURE_1hly| PDB=1hly | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''SOLUTION STRUCTURE OF HONGOTOXIN 1''' | '''SOLUTION STRUCTURE OF HONGOTOXIN 1''' | ||
| Line 38: | Line 35: | ||
[[Category: Schutz, G.]] | [[Category: Schutz, G.]] | ||
[[Category: Trieb, M.]] | [[Category: Trieb, M.]] | ||
| - | [[Category: | + | [[Category: Centruroides limbatus hgtx1]] |
| - | [[Category: | + | [[Category: Potassium channel]] |
| - | [[Category: | + | [[Category: Scorpion]] |
| - | [[Category: | + | [[Category: Toxin]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:59:45 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 15:59, 2 May 2008
SOLUTION STRUCTURE OF HONGOTOXIN 1
Overview
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.
About this Structure
1HLY is a Single protein structure of sequence from Centruroides limbatus. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Fri May 2 18:59:45 2008
