Lysosomes are membrane delimited cell organelles responsible of degradation of macromolecules. More than 50 soluble lysosomal hydrolases are known. They work as proteases, lipases, glycosidases, sulfatases and phosphatases. In addition to the classical catalytic function, lysosomes are involved in immunodefence, hormone and growth factor regulation and bone remodeling. They are of significant medical importance. Alterations in the lysosomal system are involved in many different diseases such as arthritis, allergy, multiple sceloris, altherosclerosis, Alzheimer's disease and cancer. Defects in lysosomal enzymes result in more than 40 inherited human disorders, called lysosomal storage diseases.

Our work focuses on structural studies of soluble lysosomal hydrolases. One of these is acid α-glucosidase (GAA). It hydrolases α -1,4- and α-1,6-glucosidic bonds degrading α - glucans to glucose. Lack of GAA activity in cells causes lysosomal storage disease called Pompe disease. Enzyme enhancement therapy with chemical chaperones is a potential treatment for Pompe disease. Inhibitors provide good lead compounds for the development of GAA chaperones. We have systematically studied binding of inhibitors on acid α-glucosidase and their effect on GAA stability(1). Our study provides a comparable study of the ligand properties and thus creates a basis for the design of drugs to treat Pompe disease.

(1) Bruckman C., Repo H., Koukkanen E. (2012) Systematic Structure-Activity Study on Potential Chaperone Lead Compounds for Acid α-Glucosidase. ChemMedChem 7, 1943 – 1953.