Conkazal-M1 from the MKAVA family of conotoxins - a dual-function protease inhibitor and neuroactive peptide.

ABSTRACT: Marine cone snails produce a diverse array of bioactive peptides, known as conotoxins, in their venom. Given their high target potency and specificity, conotoxins are attractive compounds for the development of precision research tools and pharmacological agents. Here, we provide the first experimental characterization of a conotoxin from the MKAVA superfamily, conkazal-M1, from Conus magus. Using NMR spectroscopy, we show that conkazal-M1 adopts a fold characteristic of the Kazal-type protease inhibitor family, featuring a Glu residue at the inhibitory P1 position. Recombinantly expressed conkazal-M1 inhibits the proteolytic activity of Subtilisin A with an apparent Ki of 1.1 μM. In addition, conkazal-M1 partially inhibits calcium transients in mouse sensory neurons, suggesting a p

SUBMITTER: Hackney CM 

PROVIDER: S-EPMC12637466 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature