Tyr13 is essential for the activity of omega-conotoxin MVIIA and GVIA, specific N-type calcium channel blockers.
Two analogs of omega-conotoxin MVIIA, a 25mer peptide neurotoxin, were synthesized by replacing Lys2 or Tyr13 with Ala. The activities of synthetic analogs were estimated from the inhibitory action on 125I-omega-conotoxin GVIA binding to chick brain synaptic plasma membranes. As in the case of omega-conotoxin GVIA, replacement of Tyr13 resulted in an enormous reduction in activity. In contrast, substitution of Ala for Lys2 gave only a small effect. These results indicate that Tyr13 is a critical amino acid of omega-conotoxin MVIIA and GVIA for blocking N-type calcium channel function.
Kim
J I
JI
Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Takahashi
M
M
Ohtake
A
A
Wakamiya
A
A
Sato
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D002645:Chickens; D002942:Circular Dichroism; D007700:Kinetics; D008239:Lysine; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D013570:Synaptic Membranes / Q000378:metabolism; D014443:Tyrosine; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D010455:Peptides; D010456:Peptides, Cyclic; D020960:omega-Conotoxins; D014443:Tyrosine; C078452:ziconotide; D020866:omega-Conotoxin GVIA; D008239:Lysine