PDBsum entry 2j25

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Hydrolase PDB id
Protein chain
497 a.a. *
SO4 ×17
Waters ×68
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Partially deglycosylated glucoceramidase
Structure: Glucosylceramidase. Chain: a, b. Fragment: residues 40-536. Synonym: beta-glucocerebrosidase, acid beta-glucosidase, d-glucosyl-n-acylsphingosine glucohydrolase, alglucerase, imiglucerase, cerezyme. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: chinese hamster ovary cells
Biol. unit: Monomer (from PDB file)
2.90Å     R-factor:   0.218     R-free:   0.273
Authors: B.Brumshtein,M.R.Wormald,I.Silman,A.H.Futerman,J.L.Sussman
Key ref:
B.Brumshtein et al. (2006). Structural comparison of differently glycosylated forms of acid-beta-glucosidase, the defective enzyme in Gaucher disease. Acta Crystallogr D Biol Crystallogr, 62, 1458-1465. PubMed id: 17139081 DOI: 10.1107/S0907444906038303
16-Aug-06     Release date:   06-Dec-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P04062  (GLCM_HUMAN) -  Glucosylceramidase
536 a.a.
497 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Glucosylceramidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: D-glucosyl-N-acylsphingosine + H2O = D-glucose + N-acylsphingosine
+ H(2)O
Bound ligand (Het Group name = BMA)
matches with 91.00% similarity
Bound ligand (Het Group name = NAG)
matches with 40.00% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   5 terms 
  Biological process     metabolic process   23 terms 
  Biochemical function     protein binding     5 terms  


DOI no: 10.1107/S0907444906038303 Acta Crystallogr D Biol Crystallogr 62:1458-1465 (2006)
PubMed id: 17139081  
Structural comparison of differently glycosylated forms of acid-beta-glucosidase, the defective enzyme in Gaucher disease.
B.Brumshtein, M.R.Wormald, I.Silman, A.H.Futerman, J.L.Sussman.
Gaucher disease is caused by mutations in the gene encoding acid-beta-glucosidase. A recombinant form of this enzyme, Cerezyme((R)), is used to treat Gaucher disease patients by ;enzyme-replacement therapy'. Crystals of Cerezyme((R)) 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((R)) 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((R)) 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.
  Selected figure(s)  
Figure 6.
Figure 6 Putative membrane binding sites in crystal structures of GlcCerase. Catalytic residues are shown in red and loops 1-3 in green. Substrate binding was modelled according to Dvir et al. (2003[Dvir, H., Harel, M., McCarthy, A. A., Toker, L., Silman, I., Futerman, A. H. & Sussman, J. L. (2003). EMBO Rep. 4, 704-709.]) and shown in yellow. (a) Some of the sulfates are shown in space-filling representation in red. (b) Side-on view [rotated 90° around the horizontal axis relative to (a)] of a putative mode of binding of GlcCerase to negatively charged phospholipids.
Figure 7.
Figure 7 Comparison of the active sites of GCase and xylanase. Residues within a 5 Å radius of the active site are displayed. Yellow, 2j25-A (GCase); green, 2j25-B; blue, 1nof (xylanase); orange, 1ogs-A (pDG-GCase); red, 1ogs-B; black, 2f61-A (pDG-GCase); grey, 2f61-B. The first number refers to residue in GCase and the second number to the corresponding residue in xylanase.
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2006, 62, 1458-1465) copyright 2006.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19741058 B.Brumshtein, P.Salinas, B.Peterson, V.Chan, I.Silman, J.L.Sussman, P.J.Savickas, G.S.Robinson, and A.H.Futerman (2010).
Characterization of gene-activated human acid-beta-glucosidase: crystal structure, glycan composition, and internalization into macrophages.
  Glycobiology, 20, 24-32.
PDB code: 2wkl
19217815 B.Liou, and G.A.Grabowski (2009).
Participation of asparagine 370 and glutamine 235 in the catalysis by acid beta-glucosidase: the enzyme deficient in Gaucher disease.
  Mol Genet Metab, 97, 65-74.  
19521672 M.R.Landon, R.L.Lieberman, Q.Q.Hoang, S.Ju, J.M.Caaveiro, S.D.Orwig, D.Kozakov, R.Brenke, G.Y.Chuang, D.Beglov, S.Vajda, G.A.Petsko, and D.Ringe (2009).
Detection of ligand binding hot spots on protein surfaces via fragment-based methods: application to DJ-1 and glucocerebrosidase.
  J Comput Aided Mol Des, 23, 491-500.  
19790257 T.S.Kang, and R.C.Stevens (2009).
Structural aspects of therapeutic enzymes to treat metabolic disorders.
  Hum Mutat, 30, 1591-1610.  
18338393 K.S.Hruska, M.E.LaMarca, C.R.Scott, and E.Sidransky (2008).
Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA).
  Hum Mutat, 29, 567-583.  
18972510 M.B.Tropak, G.J.Kornhaber, B.A.Rigat, G.H.Maegawa, J.D.Buttner, J.E.Blanchard, C.Murphy, S.J.Tuske, S.J.Coales, Y.Hamuro, E.D.Brown, and D.J.Mahuran (2008).
Identification of pharmacological chaperones for Gaucher disease and characterization of their effects on beta-glucocerebrosidase by hydrogen/deuterium exchange mass spectrometry.
  Chembiochem, 9, 2650-2662.  
18783340 Y.Kacher, B.Brumshtein, S.Boldin-Adamsky, L.Toker, A.Shainskaya, I.Silman, J.L.Sussman, and A.H.Futerman (2008).
Acid beta-glucosidase: insights from structural analysis and relevance to Gaucher disease therapy.
  Biol Chem, 389, 1361-1369.
PDB code: 2vt0
17666401 B.Brumshtein, H.M.Greenblatt, T.D.Butters, Y.Shaaltiel, D.Aviezer, I.Silman, A.H.Futerman, and J.L.Sussman (2007).
Crystal structures of complexes of N-butyl- and N-nonyl-deoxynojirimycin bound to acid beta-glucosidase: insights into the mechanism of chemical chaperone action in Gaucher disease.
  J Biol Chem, 282, 29052-29058.
PDB codes: 2v3d 2v3e
17954913 J.R.Alattia, J.E.Shaw, C.M.Yip, and G.G.Privé (2007).
Molecular imaging of membrane interfaces reveals mode of beta-glucosidase activation by saposin C.
  Proc Natl Acad Sci U S A, 104, 17394-17399.  
17524049 Y.Shaaltiel, D.Bartfeld, S.Hashmueli, G.Baum, E.Brill-Almon, G.Galili, O.Dym, S.A.Boldin-Adamsky, I.Silman, J.L.Sussman, A.H.Futerman, and D.Aviezer (2007).
Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell system.
  Plant Biotechnol J, 5, 579-590.
PDB code: 2v3f
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