PDBsum entry 2jfe

Go to PDB code: 
protein ligands links
Hydrolase PDB id
Protein chain
459 a.a. *
Waters ×158
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: The crystal structure of human cytosolic beta-glucosidase
Structure: Cytosolic beta-glucosidase. Chain: x. Synonym: human cytosolic beta-glucosidase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell: cytosolic. Expressed in: pichia pastoris. Expression_system_taxid: 4922.
2.70Å     R-factor:   0.201     R-free:   0.280
Authors: M.Czjzek,S.Tribolo,J.G.Berrin,P.A.Kroon,N.Juge
Key ref:
S.Tribolo et al. (2007). The crystal structure of human cytosolic beta-glucosidase unravels the substrate aglycone specificity of a family 1 glycoside hydrolase. J Mol Biol, 370, 964-975. PubMed id: 17555766 DOI: 10.1016/j.jmb.2007.05.034
31-Jan-07     Release date:   19-Jun-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9H227  (GBA3_HUMAN) -  Cytosolic beta-glucosidase
469 a.a.
459 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.  - Beta-glucosidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of terminal, non-reducing beta-D-glucose residues with release of beta-D-glucose.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     metabolic process   7 terms 
  Biochemical function     hydrolase activity     6 terms  


DOI no: 10.1016/j.jmb.2007.05.034 J Mol Biol 370:964-975 (2007)
PubMed id: 17555766  
The crystal structure of human cytosolic beta-glucosidase unravels the substrate aglycone specificity of a family 1 glycoside hydrolase.
S.Tribolo, J.G.Berrin, P.A.Kroon, M.Czjzek, N.Juge.
Human cytosolic beta-glucosidase (hCBG) is a xenobiotic-metabolizing enzyme that hydrolyses certain flavonoid glucosides, with specificity depending on the aglycone moiety, the type of sugar and the linkage between them. In this study, the substrate preference of this enzyme was investigated by mutational analysis, X-ray crystallography and homology modelling. The crystal structure of hCBG was solved by the molecular replacement method and refined at 2.7 A resolution. The main-chain fold of the enzyme belongs to the (beta/alpha)(8) barrel structure, which is common to family 1 glycoside hydrolases. The active site is located at the bottom of a pocket (about 16 A deep) formed by large surface loops, surrounding the C termini of the barrel of beta-strands. As for all the clan of GH-A enzymes, the two catalytic glutamate residues are located on strand 4 (the acid/base Glu165) and on strand 7 (the nucleophile Glu373). Although many features of hCBG were shown to be very similar to previously described enzymes from this family, crucial differences were observed in the surface loops surrounding the aglycone binding site, and these are likely to strongly influence the substrate specificity. The positioning of a substrate molecule (quercetin-4'-glucoside) by homology modelling revealed that hydrophobic interactions dominate the binding of the aglycone moiety. In particular, Val168, Trp345, Phe225, Phe179, Phe334 and Phe433 were identified as likely to be important in determining substrate specificity in hCBG, and site-directed mutagenesis supported a key role for some of these residues.
  Selected figure(s)  
Figure 2.
Figure 2. (a) Detailed view of the residues surrounding the glycone binding site. The position of the modelled glucose-moiety is shown. Residues potentially forming hydrogen bonds with the substrate are drawn in stick representation. The catalytic glutamate residues are coloured red. The single amino acid difference (Gln307) with respect to other GH1 β-glucosidases protrudes into the glycone binding pocket and is coloured blue. For clarity, the aglycone moiety is not represented. (b) Detailed view of the residues lining the walls of the aglycone binding pocket. The most probable position of the aglycone moiety is shown. The glycone moiety is omitted for clarity. The residues forming the hydrophobic cluster on each side of the flavonoid moiety are drawn in stick representation. This Figure was prepared using MOLSCRIPT^64 and Raster3D.^65
Figure 3.
Figure 3. Detailed view of the surface representation of hCBG, showing the position of the modelled quercetin-4′-glucoside within the active site pocket. Residues responsible for the specific form of the aglycone binding pocket are highlighted as yellow sticks. This Figure was prepared using PyMol [].
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 370, 964-975) copyright 2007.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21345211 S.Khan, T.Pozzo, M.Megyeri, S.Lindahl, A.Sundin, C.Turner, and E.N.Karlsson (2011).
Aglycone specificity of Thermotoga neapolitana β-glucosidase 1A modified by mutagenesis, leading to increased catalytic efficiency in quercetin-3-glucoside hydrolysis.
  BMC Biochem, 12, 11.  
20490603 J.R.Ketudat Cairns, and A.Esen (2010).
  Cell Mol Life Sci, 67, 3389-3405.  
19415657 C.D.Kay, P.A.Kroon, and A.Cassidy (2009).
The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products.
  Mol Nutr Food Res, 53, S92-101.  
18422657 L.M.Mendonça, and S.R.Marana (2008).
The role in the substrate specificity and catalysis of residues forming the substrate aglycone-binding site of a beta-glycosidase.
  FEBS J, 275, 2536-2547.  
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.  
19016858 R.Dopitová, P.Mazura, L.Janda, R.Chaloupková, P.Jerábek, J.Damborský, T.Filipi, N.S.Kiran, and B.Brzobohatý (2008).
Functional analysis of the aglycone-binding site of the maize beta-glucosidase Zm-p60.1.
  FEBS J, 275, 6123-6135.  
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.