PDBsum entry 2v3f

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Hydrolase PDB id
Protein chain
497 a.a. *
BTB ×2
SO4 ×12
FUC ×2
Waters ×805
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Acid-beta-glucosidase produced in carrot
Structure: Glucosylceramidase. Chain: a, b. Synonym: beta-glucocerebrosidase, acid-beta-glucosidase, d-glucosyl-n-acylsphingosine glucohydrolase, alglucerase, imiglucerase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: daucus carota. Expression_system_taxid: 4039
1.95Å     R-factor:   0.154     R-free:   0.196
Authors: 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,D.Aviezer, Israel Structural Proteomics Center(ispc)
Key ref: Y.Shaaltiel et al. (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. PubMed id: 17524049
17-Jun-07     Release date:   08-Apr-08    
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 3 residue positions (black crosses)

 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 = MAN)
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  


Plant Biotechnol J 5:579-590 (2007)
PubMed id: 17524049  
Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell system.
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, D.Aviezer.
Gaucher's disease, a lysosomal storage disorder caused by mutations in the gene encoding glucocerebrosidase (GCD), is currently treated by enzyme replacement therapy using recombinant GCD (Cerezyme) expressed in Chinese hamster ovary (CHO) cells. As complex glycans in mammalian cells do not terminate in mannose residues, which are essential for the biological uptake of GCD via macrophage mannose receptors in human patients with Gaucher's disease, an in vitro glycan modification is required in order to expose the mannose residues on the glycans of Cerezyme. In this report, the production of a recombinant human GCD in a carrot cell suspension culture is described. The recombinant plant-derived GCD (prGCD) is targeted to the storage vacuoles, using a plant-specific C-terminal sorting signal. Notably, the recombinant human GCD expressed in the carrot cells naturally contains terminal mannose residues on its complex glycans, apparently as a result of the activity of a special vacuolar enzyme that modifies complex glycans. Hence, the plant-produced recombinant human GCD does not require exposure of mannose residues in vitro, which is a requirement for the production of Cerezyme. prGCD also displays a level of biological activity similar to that of Cerezyme produced in CHO cells, as well as a highly homologous high-resolution three-dimensional structure, determined by X-ray crystallography. A single-dose toxicity study with prGCD in mice demonstrated the absence of treatment-related adverse reactions or clinical findings, indicating the potential safety of prGCD. prGCD is currently undergoing clinical studies, and may offer a new and alternative therapeutic option for Gaucher's disease.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21446960 M.Paul, and J.K.Ma (2011).
Plant-made pharmaceuticals: leading products and production platforms.
  Biotechnol Appl Biochem, 58, 58-67.  
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.  
20233333 E.P.Rybicki (2010).
Plant-made vaccines for humans and animals.
  Plant Biotechnol J, 8, 620-637.  
20673018 H.Y.Ling, A.Pelosi, and A.M.Walmsley (2010).
Current status of plant-made vaccines for veterinary purposes.
  Expert Rev Vaccines, 9, 971-982.  
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.  
20500681 J.Boothe, C.Nykiforuk, Y.Shen, S.Zaplachinski, S.Szarka, P.Kuhlman, E.Murray, D.Morck, and M.M.Moloney (2010).
Seed-based expression systems for plant molecular farming.
  Plant Biotechnol J, 8, 588-606.  
20336375 J.Marshall, K.A.McEachern, W.L.Chuang, E.Hutto, C.S.Siegel, J.A.Shayman, G.A.Grabowski, R.K.Scheule, D.P.Copeland, and S.H.Cheng (2010).
Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy.
  J Inherit Metab Dis, 33, 281-289.  
20500680 L.Faye, and V.Gomord (2010).
Success stories in molecular farming-a brief overview.
  Plant Biotechnol J, 8, 525-528.  
20668714 O.Goker-Alpan (2010).
Optimal therapy in Gaucher disease.
  Ther Clin Risk Manag, 6, 315-323.  
19956945 P.J.Weathers, M.J.Towler, and J.Xu (2010).
Bench to batch: advances in plant cell culture for producing useful products.
  Appl Microbiol Biotechnol, 85, 1339-1351.  
20673011 R.Franconi, O.C.Demurtas, and S.Massa (2010).
Plant-derived vaccines and other therapeutics produced in contained systems.
  Expert Rev Vaccines, 9, 877-892.  
21209725 T.M.Cox (2010).
Gaucher disease: clinical profile and therapeutic developments.
  Biologics, 4, 299-313.  
20233335 V.Gomord, A.C.Fitchette, L.Menu-Bouaouiche, C.Saint-Jore-Dupas, C.Plasson, D.Michaud, and L.Faye (2010).
Plant-specific glycosylation patterns in the context of therapeutic protein production.
  Plant Biotechnol J, 8, 564-587.  
20192919 Y.L.Zhang, Y.J.Wan, Z.Y.Wang, W.W.Qi, Z.R.Zhou, R.Huang, and F.Wang (2010).
Cell cycle distribution, cellular viability and mRNA expression of hGCase-gene-transfected cells in dairy goat.
  Cell Biol Int, 34, 679-685.  
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
19277123 D.Aviezer, E.Brill-Almon, Y.Shaaltiel, S.Hashmueli, D.Bartfeld, S.Mizrachi, Y.Liberman, A.Freeman, A.Zimran, and E.Galun (2009).
A plant-derived recombinant human glucocerebrosidase enzyme--a preclinical and phase I investigation.
  PLoS ONE, 4, e4792.  
18983932 E.P.Rybicki (2009).
Plant-produced vaccines: promise and reality.
  Drug Discov Today, 14, 16-24.  
19836291 H.Daniell, N.D.Singh, H.Mason, and S.J.Streatfield (2009).
Plant-made vaccine antigens and biopharmaceuticals.
  Trends Plant Sci, 14, 669-679.  
19229568 R.Appels (2009).
Diversity of genome research at the 2009 Plant and Animal Genome Conference.
  Funct Integr Genomics, 9, 1-6.  
19461852 B.Brumshtein, H.M.Greenblatt, A.H.Futerman, I.Silman, and J.L.Sussman (2008).
Control of the rate of evaporation in protein crystallization by the 'microbatch under oil' method.
  J Appl Crystallogr, 41, 969-971.  
18321157 G.A.Grabowski (2008).
Treatment perspectives for the lysosomal storage diseases.
  Expert Opin Emerg Drugs, 13, 197-211.  
18413899 H.Du, T.L.Cameron, S.J.Garger, G.P.Pogue, L.A.Hamm, E.White, K.M.Hanley, and G.A.Grabowski (2008).
Wolman disease/cholesteryl ester storage disease: efficacy of plant-produced human lysosomal acid lipase in mice.
  J Lipid Res, 49, 1646-1657.  
18627336 N.J.Weinreb (2008).
Imiglucerase and its use for the treatment of Gaucher's disease.
  Expert Opin Pharmacother, 9, 1987-2000.  
18729283 T.Winckler (2008).
[Enzyme replacement therapy for Gaucher's Disease]
  Pharm Unserer Zeit, 37, 352-353.  
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
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.