title: Binding of six chimeric analogs of omega-conotoxin MVIIA and MVIIC to N- and P/Q-type calcium channels.
abstract: 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.
authors.affiliation: Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo, 194-8511, Japan. kazuki@libra.ls.m-kagaku.co.jp
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: C
authors.initials: C
authors.lastname: Raymond
authors.forename: N
authors.initials: N
authors.lastname: Martin-Moutot
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.forename: A
authors.initials: A
authors.lastname: Ohtake
authors.forename: K
authors.initials: K
authors.lastname: Minami
authors.forename: C
authors.initials: C
authors.lastname: Van Renterghem
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: M J
authors.initials: MJ
authors.lastname: Seagar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000378:metabolism; D015220:Calcium Channels / Q000145:classification / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000378:metabolism; D020907:Calcium Channels, Q-Type / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002942:Circular Dichroism; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020960:omega-Conotoxins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D011993:Recombinant Fusion Proteins; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; C078452:ziconotide