2J25

Partially deglycosylated glucoceramidase

Summary for 2J25

• Entry DOI: 10.2210/pdb2j25/pdb
• Related: 1OGS 1Y7V 2F61
• Descriptor: GLUCOSYLCERAMIDASE, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: pharmaceutical, gaucher disease, disease mutation, glycosidase, sphingolipid, polymorphism, glycoprotein, membrane, lysosome, hydrolase, glucosidase, glucocerebrosidase, alternative initiation, lipid metabolism, cerezyme hydrolase, sphingolipid metabolism
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 115480.78

Authors

Brumshtein, B.,Wormald, M.R.,Silman, I.,Futerman, A.H.,Sussman, J.L. (deposition date: 2006-08-16, release date: 2006-12-06, Last modification date: 2024-10-09)

Primary citation

Brumshtein, B.,Wormald, M.R.,Silman, I.,Futerman, A.H.,Sussman, J.L.
Structural Comparison of Differently Glycosylated Forms of Acid-Beta-Glucosidase, the Defective Enzyme in Gaucher Disease
Acta Crystallogr.,Sect.D, 62:1458-, 2006

PubMed Abstract: 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.

PubMed: 17139081
DOI: 10.1107/S0907444906038303

Experimental method

X-RAY DIFFRACTION (2.9 Å)