Replacement of the N-terminal half of omega-conotoxin MVIIC, a peptide blocker 
of P/Q-type calcium channels, with that of omega-conotoxin MVIIA significantly 
increased the affinity for N-type calcium channels. To identify the residues 
essential for subtype selectivity, we examined single reverse mutations from 
MVIIA-type to MVIIC-type in this chimeric analog. A reverse mutation from Lys(7) 
to Pro(7) decreased the affinity for both P/Q- and N-type channels, whereas that 
from Leu(11) to Thr(11) increased the affinity for P/Q-type channels and 
decreased the affinity for N-type channels. The roles of these two residues were 
confirmed by synthesizing two MVIIC analogs in which Pro(7) and Thr(11) were 
replaced with Lys(7) and Leu(11), respectively.