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1ogs
From Proteopedia
| 1ogs, resolution 2.00Å () | |||||||||
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| Sites: | |||||||||
| Ligands: | , | ||||||||
| Non-Standard Residues: | |||||||||
| Activity: | Glucosylceramidase, with EC number 3.2.1.45 | ||||||||
| Domains: | Glyco_hydro_30, COG5520 | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB, TOPSAN | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Human acid-beta-glucosidase
(see also Treatment of Gaucher disease)
Gaucher disease, the most common lysosomal storage disease, is caused by mutations in the gene that encodes acid-beta-glucosidase (GlcCerase). Type 1 is characterized by hepatosplenomegaly, and types 2 and 3 by early or chronic onset of severe neurological symptoms. No clear correlation exists between the approximately 200 GlcCerase mutations and disease severity, although homozygosity for the common mutations N370S and L444P is associated with non- neuronopathic and neuronopathic disease, respectively. We report the X-ray structure of GlcCerase at 2.0 A resolution. The catalytic domain consists of a (beta/alpha)(8) TIM barrel, as expected for a member of the glucosidase hydrolase A clan. The distance between the catalytic residues E235 and E340 is consistent with a catalytic mechanism of retention. N370 is located on the longest alpha-helix (helix 7), which has several other mutations of residues that point into the TIM barrel. Helix 7 is at the interface between the TIM barrel and a separate immunoglobulin-like domain on which L444 is located, suggesting an important regulatory or structural role for this non-catalytic domain. The structure provides the possibility of engineering improved GlcCerase for enzyme-replacement therapy, and for designing structure-based drugs aimed at restoring the activity of defective GlcCerase.
X-ray structure of human acid-beta-glucosidase, the defective enzyme in Gaucher disease., Dvir H, Harel M, McCarthy AA, Toker L, Silman I, Futerman AH, Sussman JL, EMBO Rep. 2003 Jul;4(7):704-9. PMID:12792654
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Overview
Gaucher disease, the most common lysosomal storage disease, is caused by mutations in the gene that encodes acid-beta-glucosidase (E.C. 3.2.1.45, GlcCerase). Type 1 is characterized by hepatosplenomegaly, and types 2 and 3 by early or chronic onset of severe neurological symptoms. The correlation between the ~ 200 mutations in GlcCerase and disease severity is not completely understood, although homozygosity for the common is associated with non-neuronopathic and neuronopathic disease, respectively. The X-ray structure of GlcCerase at was resolved at 2.0 A resolution. The catalytic domain consists of a (beta/alpha)(8) TIM barrel, as expected for a member of the glucosidase hydrolase A family. The distance between the is consistent with a catalytic mechanism of retention. N370 is located on the longest alpha-helix (), which has several other mutations of residues that point into the TIM barrel. Helix 7 is at the interface between the and a separate on which L444 is located, suggesting an important regulatory or structural role for this non-catalytic domain. The structure provides the possibility of engineering improved GlcCerase for enzyme-replacement therapy, and for designing structure-based drugs aimed at restoring the activity of defective GlcCerase
About this Structure
1OGS is a Single protein structure. Full crystallographic information is available from OCA.
Reference
X-ray structure of human acid-beta-glucosidase, the defective enzyme in Gaucher disease., Dvir H, Harel M, McCarthy AA, Toker L, Silman I, Futerman AH, Sussman JL, EMBO Rep. 2003 Jul;4(7):704-9. PMID:12792654 Page seeded by OCA on Sun Apr 13 09:42:40 2008
Proteopedia Page Contributors and Editors (what is this?)
OCA, Alexander Berchansky, Eran Hodis, Michal Harel, Jaime Prilusky
Categories: Glucosylceramidase | Single protein | Dvir, H. | Futerman, A H. | Harel, M. | ISPC, Israel Structural Proteomics Center. | Mccarthy, A A. | Silman, I. | Sussman, J L. | Toker, L. | Alternative initiation | Cerezyme hydrolase | Disease mutati polymorphism | Gaucher disease | Glucocerebrosidase | Glucosidase | Glycoprote lysosome | Glycosidase | ISPC | Israel Structural Proteomics Center | Membrane | Pharmaceutical | Signal | Sphingolipid metabolism | Structural genomic
