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From Proteopedia

1ogs, resolution 2.00Å ()
Sites:
Ligands:	,
Non-Standard Residues:
Activity:	Glucosylceramidase, with EC number 3.2.1.45
Domains:	Glyco_hydro_30, COG5520
Structural annotation: Resources: CATH : 1Ogsa02, 1Ogsa01, 1Ogsb02, 1Ogsb01 InterPro : Ipr001139, Ipr013781 Pfam : PF02055 SCOP : d1ogsa1, d1ogsa2, d1ogsb1, d1ogsb2 UniProt : P04062
Functional annotation: Resources: GeneCard : GBA Cellular component: membrane lysosome Biological process: sphingolipid metabolic process lipid metabolic process carbohydrate metabolic process lysosome organization and biogenesis metabolic process Molecular function: hydrolase activity hydrolase activity, acting on glycosyl bonds catalytic activity glucosylceramidase activity cation binding
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats Explanation Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, PDBsum, RCSB, TOPSAN
Coordinates:	save as pdb, mmCIF, xml

Human acid-beta-glucosidase

Overview

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 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 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