2VT0

X-ray structure of a conjugate with conduritol-beta-epoxide of acid-beta-glucosidase overexpressed in cultured plant cells

Summary for 2VT0

• Entry DOI: 10.2210/pdb2vt0/pdb
• Descriptor: GLUCOSYLCERAMIDASE, alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-3)]2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-L-fucopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: hydrolase, alternative initiation, sphingolipid metabolism, israel structural proteomics center, disease mutation, glucocerebrosidase, pharmaceutical, gaucher disease, lipid metabolism, glucosidase, glycosidase, polymorphism, glycoprotein, ispc, membrane, cerezyme, lysosome, structural genomics, alternative splicing
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 115802.74

Authors

Brumshtein, B.,Greenblatt, H.M.,Shaaltiel, Y.,Aviezer, D.,Silman, I.,Futerman, A.H.,Sussman, J.L. (deposition date: 2008-05-03, release date: 2008-09-23, Last modification date: 2024-10-23)

Primary citation

Kacher, Y.,Brumshtein, B.,Boldin-Adamsky, S.,Toker, L.,Shainskaya, A.,Silman, I.,Sussman, J.L.,Futerman, A.H.
Acid Beta-Glucosidase: Insights from Structural Analysis and Relevance to Gaucher Disease Therapy.
Biol.Chem., 389:1361-, 2008

PubMed Abstract: In mammalian cells, glucosylceramide (GlcCer), the simplest glycosphingolipid, is hydrolyzed by the lysosomal enzyme acid beta-glucosidase (GlcCerase). In the human metabolic disorder Gaucher disease, GlcCerase activity is significantly decreased owing to one of approximately 200 mutations in the GlcCerase gene. The most common therapy for Gaucher disease is enzyme replacement therapy (ERT), in which patients are given intravenous injections of recombinant human GlcCerase; the Genzyme product Cerezyme has been used clinically for more than 15 years and is administered to approximately 4000 patients worldwide. Here we review the crystal structure of Cerezyme and other recombinant forms of GlcCerase, as well as of their complexes with covalent and non-covalent inhibitors. We also discuss the stability of Cerezyme, which can be altered by modification of its N-glycan chains with possible implications for improved ERT in Gaucher disease.

PubMed: 18783340
DOI: 10.1515/BC.2008.163

Experimental method

X-RAY DIFFRACTION (2.15 Å)