Protein Structure And The Molecular Basis Of Schindler A

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Abstract

The degradation of cellular molecules is a normal process that can go awry. Defects in the degradation of various cell macromolecules cause disease and are usually the result of mutations in specific enzymes. Two key enzymes in the degradation of cellular carbohydrates are alpha-N-acetylgalactosaminidase and alpha-galactosidase. Mutations in these enzymes cause Shindler and Fabry diseases, respectively. We have determined the structure of alpha-N-acetylgalactosaminidase by x-ray diffraction techniques and have constructed a model of the closely-related alpha-galactosidase enzyme. We have mapped the locations of mutations that give rise to Shindler and Fabry diseases and have begun to describe the catalytic mechanisms by which the enzymes perform their normal function of carbohydrate degradation.