Journal article
Acid beta-glucosidase: insights from structural analysis and relevance to Gaucher disease therapy
Biological Chemistry, Vol.389(11), pp.1361-1369
Nov/2008
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 (R) 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 (R) 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 (R), which can be altered by modification of its N-glycan chains with possible implications for improved ERT in Gaucher disease.
Details
- Title
- Acid beta-glucosidase; insights from structural analysis and relevance to Gaucher disease therapy
- Creators
- Yaacov Kacher (null)Boris Brumshtein (null) - 972WIS_INST___9Swetlana Boldin-Adamsky (null)Lilly Toker (null)Alla Shainskaya (null) - 972WIS_INST___113Israel Silman (null) - 972WIS_INST___123Joel Sussman (null) - 972WIS_INST___9Anthony H. Futerman (null) - 972WIS_INST___112
- Resource Type
- Journal article; Review
- Publication Details
- Biological Chemistry, Vol.389(11), pp.1361-1369; Nov/2008
- Number of pages
- 9
- Language
- English
- DOI
- https://doi.org/10.1515/BC.2008.163
- Grant note
- Magneton Program, Office of the Chief Scientist, Ministry of Industry and Commerce, Israel; National Gaucher Foundation; Gaucher Disease Divot Classic of Chicago; Benoziyo Center for NeuroscienceWork in the authors' laboratories was supported by the Magneton Program, Office of the Chief Scientist, Ministry of Industry and Commerce, Israel, the National Gaucher Foundation, the Gaucher Disease Divot Classic of Chicago, and the Benoziyo Center for Neuroscience. We thank Tevie Mehlman for help with MS analysis. J.L. Sussman is the Morton and Gladys Pickman Professor of Structural Biology, and A. H. Futerman is the Joseph Meyerhoff Professor of Biochemistry at the Weizmann Institute of Science._ALMAME_DELIMITER_
- Record Identifier
- 993264016903596
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