Structural Biology of Glycoproteins in Human Disease
Research in our lab focuses on structural biology of glycoproteins, particularly those implicated in human disease. For instance, deficiencies in lysosomal enzymes result in the accumulation of their substrates, which eventually leads to the symptoms of lysosomal storage diseases (a family containing over 40 members including Gaucher, Tay-Sachs, and Fabry diseases). We have determined the x-ray crystallographic structures of two lysosomal glycosidases, α-N-acetylgalactosaminidase (α-NAGAL) and α-galactosidase (α-GAL), as well as complexes with their catalytic products. The structures revealed the locations of the hundreds of individual point mutations leading to Schindler and Fabry diseases.
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