2011/04/13

Intracellular Rescue of the Uroporphyrinogen III Synthase Activity in Enzymes Carrying the Hotspot Mutation

In a collaborative effort between the Metabolomics Unit and the Structural Biology Unit, CICbioGUNE researchers have unravelled the mechanism by which the most aggressive mutation found in uroporphyrinogen III synthase enzyme gene produces congenital erythropoietic porphyria. Upon mutation, the protein unfolds and form aggregates that are eliminated from the cell via the proteasome. After inhibiting this degradation route, the mutant protein recovers the intracellular activity, paving the way for a new line of therapeutic intervention. This work has been published in the current issue of the Journal of Biological Chemistry