Structure of the analgesic mu-conotoxin KIIIA and effects on the structure and function of disulfide deletion.

ABSTRACT: Mu-conotoxin mu-KIIIA, from Conus kinoshitai, blocks mammalian neuronal voltage-gated sodium channels (VGSCs) and is a potent analgesic following systemic administration in mice. We have determined its solution structure using NMR spectroscopy. Key residues identified previously as being important for activity against VGSCs (Lys7, Trp8, Arg10, Asp11, His12, and Arg14) all reside on an alpha-helix with the exception of Arg14. To further probe structure-activity relationships of this toxin against VGSC subtypes, we have characterized the analogue mu-KIIIA[C1A,C9A], in which the Cys residues involved in one of the three disulfides in mu-KIIIA were replaced with Ala. Its structure is quite similar to that of mu-KIIIA, indicating that the Cys1-Cys9 disulfide bond could be removed without any si

SUBMITTER: Khoo KK 

PROVIDER: S-EPMC4153535 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature