Conformational studies of a melittin-inhibitor complex

The conformation of a melittin-inhibitor complex was studied by solution NM R, solid-state NMR, and circular dichroism. In solution, binding was studie d by titrating inhibitor against melittin in dimethyl sulfoxide, methanol, aqueous buffer, and dodecylphosphocholine micelles. The change in chemical shift of Trp19 resonances and the formation of a precipitate at 1:1 molar r atio indicated that the inhibitor was bound to melittin. Solid-state NMR al so showed a change in chemical shift of two labeled carbons of melittin nea r Pro14 and a change in H-1 T-1 relaxation times when complexed with inhibi tor. Rotational resonance experiments of melittin labeled in the proline re gion indicated a change in conformation for melittin complexed with inhibit or. This observation was also supported by circular dichroism measurements, indicating a reduction in alpha -helical structure for increasing ratios o f inhibitor bound to melittin.