PDBsum entry 2vt0

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Hydrolase PDB id
Protein chain
495 a.a. *
CBU ×2
SO4 ×10
FUC ×2
Waters ×464
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: X-ray structure of a conjugate with conduritol-beta-epoxide of acid-beta-glucosidase overexpressed in cultured plant cells
Structure: Glucosylceramidase. Chain: a, b. Fragment: tim barrel glucosidase, residues 40-536. Synonym: beta-glucocerebrosidase, acid beta-glucosidase, d-glucosyl-n-acylsphingosine glucohydrolase, glucosidase. Engineered: yes. Other_details: the enzyme is covalently inhibited by cbe
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: lysosome. Expressed in: daucus carota. Expression_system_taxid: 4039
2.15Å     R-factor:   0.154     R-free:   0.201
Authors: B.Brumshtein,H.M.Greenblatt,Y.Shaaltiel,D.Aviezer,I.Silman, A.H.Futerman,J.L.Sussman
Key ref: Y.Kacher et al. (2008). Acid beta-glucosidase: insights from structural analysis and relevance to Gaucher disease therapy. Biol Chem, 389, 1361-1369. PubMed id: 18783340
03-May-08     Release date:   23-Sep-08    
Go to PROCHECK summary

Protein chains
No UniProt id for this chain
Struc: 495 a.a.
Key:    Secondary structure  CATH domain

 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 = CBU)
matches with 91.67% similarity
Bound ligand (Het Group name = NAG)
matches with 40.74% 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   22 terms 
  Biochemical function     protein binding     5 terms  


Biol Chem 389:1361-1369 (2008)
PubMed id: 18783340  
Acid beta-glucosidase: insights from structural analysis and relevance to Gaucher disease therapy.
Y.Kacher, B.Brumshtein, S.Boldin-Adamsky, L.Toker, A.Shainskaya, I.Silman, J.L.Sussman, A.H.Futerman.
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.

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
20945356 C.E.Bobst, J.J.Thomas, P.A.Salinas, P.Savickas, and I.A.Kaltashov (2010).
Impact of oxidation on protein therapeutics: conformational dynamics of intact and oxidized acid-β-glucocerebrosidase at near-physiological pH.
  Protein Sci, 19, 2366-2378.  
20534487 C.P.Phenix, B.P.Rempel, K.Colobong, D.J.Doudet, M.J.Adam, L.A.Clarke, and S.G.Withers (2010).
Imaging of enzyme replacement therapy using PET.
  Proc Natl Acad Sci U S A, 107, 10842-10847.  
20574770 J.B.Novo, M.L.Oliveira, G.S.Magalhães, L.Morganti, I.Raw, and P.L.Ho (2010).
Generation of polyclonal antibodies against recombinant human glucocerebrosidase produced in Escherichia coli.
  Mol Biotechnol, 46, 279-286.  
21079602 M.D.Witte, W.W.Kallemeijn, J.Aten, K.Y.Li, A.Strijland, W.E.Donker-Koopman, A.M.van den Nieuwendijk, B.Bleijlevens, G.Kramer, B.I.Florea, B.Hooibrink, C.E.Hollak, R.Ottenhoff, R.G.Boot, G.A.van der Marel, H.S.Overkleeft, and J.M.Aerts (2010).
Ultrasensitive in situ visualization of active glucocerebrosidase molecules.
  Nat Chem Biol, 6, 907-913.  
20505772 Y.H.Xu, Y.Sun, S.Barnes, and G.A.Grabowski (2010).
Comparative therapeutic effects of velaglucerase alfa and imiglucerase in a Gaucher disease mouse model.
  PLoS One, 5, e10750.  
19437524 B.Brumshtein, M.Aguilar-Moncayo, M.I.García-Moreno, C.Ortiz Mellet, J.M.García Fernández, I.Silman, Y.Shaaltiel, D.Aviezer, J.L.Sussman, and A.H.Futerman (2009).
6-Amino-6-deoxy-5,6-di-N-(N'-octyliminomethylidene)nojirimycin: synthesis, biological evaluation, and crystal structure in complex with acid beta-glucosidase.
  Chembiochem, 10, 1480-1485.
PDB code: 2wcg
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.  
19717598 Y.G.Kim, J.H.Kim, and K.J.Kim (2009).
Crystal structure of the Salmonella enterica serovar typhimurium virulence factor SrfJ, a glycoside hydrolase family enzyme.
  J Bacteriol, 191, 6550-6554.
PDB code: 2wnw
19014345 E.Gulbins (2008).
Highlight: sphingolipids - signals and disease.
  Biol Chem, 389, 1347-1348.  
  882348 Novikova Ech (1977).
[International Children's Day]
  Pediatriia, (), 3-7.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.