Crystallization and preliminary X-ray analysis of recombinant human acid β-glucocerebrosidase, a treatment for Gaucher's disease

Acid β-glucocerebrosidase (N-acylsphingosyl-1-O-β-D-glucoside:glucohydrolase) is a lysosomal glycoprotein that catalyzes the hydrolysis of the glycolipid glucocerebroside to glucose and ceramide. Inadequate levels of this enzyme underly the pathophysiology of Gaucher's disease. Cerezyme (Genzyme Corporation, Cambridge, MA, USA) is a partially deglycosylated form of recombinant human acid β-glucocerebrosidase that is used in the treatment of Gaucher patients. Although acid β-glucocerebrosidase belongs to a large family of glycosidases, relatively little is known regarding its structural biology. Here, the crystallization and the initial diffraction analysis of Cerezyme are reported. The crystals are C-centered orthorhombic, with unit-cell parameters a = 285.0, b = 110.2, c = 91.7 Å. A 99.9% complete data set has been collected to 2.75 Å with an R_sym of 8.8%.