| Autor: |
Paul K. Pallaghy, James A. Angus, James P. Flinn, Raymond S. Norton, Sarah L. Whorlow, Roger Murphy, Christine E. Wright, Michael J. Lew |
| Rok vydání: |
1997 |
| Předmět: |
|
| Zdroj: |
Journal of Biological Chemistry. 272:12014-12023 |
| ISSN: |
0021-9258 |
| DOI: |
10.1074/jbc.272.18.12014 |
| Popis: |
The structure-function relationships of the N-type calcium channel blocker, ω-conotoxin GVIA (GVIA), have been elucidated by structural, binding and in vitro and in vivo functional studies of alanine-substituted analogues of the native molecule. Alanine was substituted at all non-bridging positions in the sequence. In most cases the structure of the analogues in aqueous solution was shown to be native-like by 1H NMR spectroscopy. Minor conformational changes observed in some cases were characterized by two-dimensional NMR. Replacement of Lys2and Tyr13 with Ala caused reductions in potency of more than 2 orders of magnitude in three functional assays (sympathetic nerve stimulation of rat isolated vas deferens, right atrium and mesenteric artery) and a rat brain membrane binding assay. Replacement of several other residues with Ala (particularly Arg17, Tyr22 and Lys24) resulted in significant reductions in potency ( |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
