Molecular Structure of Charybdotoxin, a Pore-Directed Inhibitor of Potassium Ion Channels
| Autor: | Walter Massefski, Christopher Miller, Alfred G. Redfield, Dennis R. Hare |
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| Rok vydání: | 1990 |
| Předmět: |
Models
Molecular Magnetic Resonance Spectroscopy Potassium Channels Multidisciplinary Charybdotoxin Protein Conformation Molecular Sequence Data Analytical chemistry Beta sheet Scorpion Venoms Nuclear Overhauser effect Antiparallel (biochemistry) NMR spectra database chemistry.chemical_compound Crystallography chemistry Side chain Amino Acid Sequence Disulfides Spectroscopy Two-dimensional nuclear magnetic resonance spectroscopy |
| Zdroj: | Science. 249:521-524 |
| ISSN: | 1095-9203 0036-8075 |
| Popis: | The three-dimensional structure of charybdotoxin, a high-affinity peptide blocker of several potassium ion channels, was determined by two-dimensional nuclear magnetic resonance (2-D NMR) spectroscopy. Unambiguous NMR assignments of backbone and side chain hydrogens were made for all 37 amino acids. The structure was determined by distance geometry and refined by nuclear Overhauser and exchange spectroscopy back calculation. The peptide is built on a foundation of three antiparallel beta strands to which other parts of the sequence are attached by three disulfide bridges. The overall shape is roughly ellipsoidal, with axes of approximately 2.5 and 1.5 nanometers. Nine of the ten charged groups are located on one side of the ellipsoid, with seven of the eight positive residues lying in a stripe 2.5 nanometers in length. The other side displays three hydrophobic residues projecting prominently into aqueous solution. The structure rationalizes several mechanistic features of charybdotoxin block of the high-conductance Ca2(+)-activated K+ channel. |
| Databáze: | OpenAIRE |
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