The Tetrodotoxin Binding Site Is within the Outer Vestibule of the Sodium Channel

Marine Drugs

Harry A. Fozzard¹ 

关键词: marine toxins;    Na channels;    molecular modeling;   

DOI  :  10.3390/md8020219

来源: mdpi

【 摘 要 】

Tetrodotoxin and saxitoxin are small, compact asymmetrical marine toxins that block voltage-gated Na channels with high affinity and specificity. They enter the channel pore’s outer vestibule and bind to multiple residues that control permeation. Radiolabeled toxins were key contributors to channel protein purification and subsequent cloning. They also helped identify critical structural elements called P loops. Spacial organization of their mutation-identified interaction sites in molecular models has generated a molecular image of the TTX binding site in the outer vestibule and the critical permeation and selectivity features of this region. One site in the channel’s domain I P loop determines affinity differences in mammalian isoforms.

【 授权许可】

CC BY   
© 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland