Deciphering the substrate identity and catalytic mode of human PREPL

PREPL (Prolyl endopeptidase-like) is a protein involved in mitochondrial homeostasis. In humans, PREPL deficiency causes a recessive metabolic disorder called congenital myasthenic syndrome-22. Previously, our collaborators in the lab of Prof. J. Creemers in Louven, Belgium, have shown that PREPL has (thio)esterase activity and plays a role in regulating mitochondrial gene expression and mitochondrial complex activities (Rosier et al. 2021). We subsequently solved the crystal structure that provided insight into the mechanism of action of this enzyme. We are currently studying the underlying molecular reasons for it being an esterase, not a peptidase.

Rosier et al. 2021 Prolyl endopeptidase-like is a (thio)esterase involved in mitochondrial respiratory chain function. iScience. DOI : 10.1016/j.isci.2021.103460.