Evolution of a protein fold from toxin to physiological regulator: an endogenous potassium channel blocker in humans

Dea anemones produce a family of potent potassium channel blockers with a unique structure known as the ShK fold. Genome analyses reveal that this ShK domain is also present in many proteins from higher organisms, although in most of these proteins its biological function has not been defined. the aims of this project are to investigate the structure, structure-function relationships and physiological roles of this stable fold in a unique human protein containing this motif, matrix metalloprotease 23. Matrix metalloprotease 23 has possible roles in prostate and other cancers, and out results will elucidate the role of the ShK domain in these pathologies.