2j25

Gaucher disease is caused by mutations in the gene encoding acid-beta-glucosidase. A recombinant form of this enzyme, Cerezyme, is used to treat Gaucher disease patients by ;enzyme-replacement therapy'. Crystals of Cerezyme after its partial deglycosylation were obtained earlier and the structure was solved to 2.0 A resolution [Dvir et al. (2003), EMBO Rep. 4, 704-709]. The crystal structure of unmodified Cerezyme is now reported, in which a substantial number of sugar residues bound to three asparagines via N-glycosylation could be visualized. The structure of intact fully glycosylated Cerezyme is virtually identical to that of the partially deglycosylated enzyme. However, the three loops at the entrance to the active site, which were previously observed in alternative conformations, display additional variability in their structures. Comparison of the structure of acid-beta-glucosidase with that of xylanase, a bacterial enzyme from a closely related protein family, demonstrates a close correspondence between the active-site residues of the two enzymes.

Structural comparison of differently glycosylated forms of acid-beta-glucosidase, the defective enzyme in Gaucher disease., Brumshtein B, Wormald MR, Silman I, Futerman AH, Sussman JL, Acta Crystallogr D Biol Crystallogr. 2006 Dec;62(Pt 12):1458-65. Epub 2006, Nov 23. PMID:17139081

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA

Categories: Glucosylceramidase | Homo sapiens | Brumshtein, B. | Futerman, A H. | Silman, I. | Sussman, J L. | Wormald, M R. | Alternative initiation | Cerezyme hydrolase | Disease mutation | Gaucher disease | Glucocerebrosidase | Glucosidase | Glycoprotein | Glycosidase | Hydrolase | Lipid metabolism | Lysosome | Membrane | Sphingolipid | Sphingolipid metabolism