Identification of Three Separate Binding Sites on SHK Toxin, a Potent Inhibitor of Voltage-Dependent Potassium Channels in Human T-Lymphocytes and Rat Brain
| Autor: | I. Zaydenberg, Michael W. Pennington, William R. Kem, Ilya Khaytin, K. Crowley, D.S. Krafte, V.M. Mahnir, M. E. Byrnes |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Potassium Channels
T-Lymphocytes Molecular Sequence Data Biophysics Clostridium difficile toxin A medicine.disease_cause Biochemistry Jurkat cells Cell Line Membrane Potentials Structure-Activity Relationship Cnidarian Venoms Potassium Channel Blockers medicine Animals Humans Amino Acid Sequence Binding site Molecular Biology Membrane potential Binding Sites Sequence Homology Amino Acid Stichodactyla helianthus biology Toxin Brain Potassium channel blocker Cell Biology biology.organism_classification Potassium channel Rats Peptides medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 219:696-701 |
| ISSN: | 0006-291X |
| DOI: | 10.1006/bbrc.1996.0297 |
| Popis: | Eighteen synthetic analogs of ShK toxin, a thirty-five residue K channel blocker derived from the sea anemone Stichodactyla helianthus, were prepared in order to identify functionally important residues. CD spectra of sixteen of the analogs were virtually identical with the spectrum of wild-type toxin, indicating that the conformations were not affected by the substitutions. A conserved residue, Lys22, is essential for ShK binding to rat brain K channels which are primarily of the Kv1.2 type. However, a cationic side chain at position 22 is not essential for binding to the human Jurkat T-lymphocyte Kv1.3 channel. While decreasing bulkiness at this position affected toxin affinity for the brain K channels, increasing bulkiness decreased toxin affinity for both brain and lymphocyte K channels. In contrast to the rat brain channels, ShK binding to Kv1.3 was sensitive to substitution at Lys9 and Arg11. |
| Databáze: | OpenAIRE |
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