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PDBsum entry 2ces

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protein ligands metals links
Hydrolase PDB id
2ces
Jmol
Contents
Protein chains
440 a.a. *
Ligands
ACT ×2
GIM ×2
Metals
_CA
Waters ×476
* Residue conservation analysis
PDB id:
2ces
Name: Hydrolase
Title: Beta-glucosidase from thermotoga maritima in complex with glucoimidazole
Structure: Beta-glucosidase a. Chain: a, b. Synonym: gentiobiase, cellobiase, beta-d-glucoside glucohydrolase. Engineered: yes
Source: Thermotoga maritima. Organism_taxid: 2336. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Resolution:
2.15Å     R-factor:   0.194     R-free:   0.247
Authors: T.M.Gloster,S.Roberts,A.Vasella,G.J.Davies
Key ref: T.M.Gloster et al. (2006). Structural, kinetic, and thermodynamic analysis of glucoimidazole-derived glycosidase inhibitors. Biochemistry, 45, 11879-11884. PubMed id: 17002288 DOI: 10.1021/bi060973x
Date:
10-Feb-06     Release date:   27-Sep-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q08638  (BGLA_THEMA) -  Beta-glucosidase A
Seq:
Struc:
446 a.a.
440 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.2.1.21  - 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!
  Biological process     metabolic process   4 terms 
  Biochemical function     hydrolase activity     4 terms  

 

 
DOI no: 10.1021/bi060973x Biochemistry 45:11879-11884 (2006)
PubMed id: 17002288  
 
 
Structural, kinetic, and thermodynamic analysis of glucoimidazole-derived glycosidase inhibitors.
T.M.Gloster, S.Roberts, G.Perugino, M.Rossi, M.Moracci, N.Panday, M.Terinek, A.Vasella, G.J.Davies.
 
  ABSTRACT  
 
Inhibition of glycosidases has great potential in the quest for highly potent and specific drugs to treat diseases such as diabetes, cancer, and viral infections. One of the most effective ways of designing such compounds is by mimicking the transition state. Here we describe the structural, kinetic, and thermodynamic dissection of binding of two glucoimidazole-derived compounds, which are among the most potent glycosidase inhibitors reported to date, with two family 1 beta-glycosidases. Provocatively, while inclusion of the phenethyl moiety improves binding by a factor of 20-80-fold, this does not appear to result from better noncovalent interactions with the enzyme; instead, improved affinity may be derived from significantly better entropic contributions to binding displayed by the phenethyl-substituted imidazole compound.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20730780 A.M.Abdula, R.A.Khalaf, M.S.Mubarak, and M.O.Taha (2011).
Discovery of new β-D-galactosidase inhibitors via pharmacophore modeling and QSAR analysis followed by in silico screening.
  J Comput Chem, 32, 463-482.  
20490878 R.A.Khalaf, A.M.Abdula, M.S.Mubarak, and M.O.Taha (2011).
Discovery of new β-D: -glucosidase inhibitors via pharmacophore modeling and QSAR analysis followed by in silico screening.
  J Mol Model, 17, 443-464.  
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.  
21420868 T.Li, L.Guo, Y.Zhang, J.Wang, Z.Zhang, J.Li, W.Zhang, J.Lin, W.Zhao, and P.G.Wang (2011).
Structure-activity relationships in a series of C2-substituted gluco-configured tetrahydroimidazopyridines as β-glucosidase inhibitors.
  Bioorg Med Chem, 19, 2136-2144.  
20376631 C.S.Park, M.H.Yoo, K.H.Noh, and D.K.Oh (2010).
Biotransformation of ginsenosides by hydrolyzing the sugar moieties of ginsenosides using microbial glycosidases.
  Appl Microbiol Biotechnol, 87, 9.  
20490603 J.R.Ketudat Cairns, and A.Esen (2010).
β-Glucosidases.
  Cell Mol Life Sci, 67, 3389-3405.  
20066263 T.M.Gloster, and G.J.Davies (2010).
Glycosidase inhibition: assessing mimicry of the transition state.
  Org Biomol Chem, 8, 305-320.  
19499593 M.D.Balcewich, K.A.Stubbs, Y.He, T.W.James, G.J.Davies, D.J.Vocadlo, and B.L.Mark (2009).
Insight into a strategy for attenuating AmpC-mediated beta-lactam resistance: structural basis for selective inhibition of the glycoside hydrolase NagZ.
  Protein Sci, 18, 1541-1551.
PDB codes: 2wca 3gs6 3gsm
18615662 A.D.Hill, and P.J.Reilly (2008).
Computational analysis of glycoside hydrolase family 1 specificities.
  Biopolymers, 89, 1021-1031.  
18558099 D.J.Vocadlo, and G.J.Davies (2008).
Mechanistic insights into glycosidase chemistry.
  Curr Opin Chem Biol, 12, 539-555.  
18408714 L.E.Tailford, W.A.Offen, N.L.Smith, C.Dumon, C.Morland, J.Gratien, M.P.Heck, R.V.Stick, Y.Blériot, A.Vasella, H.J.Gilbert, and G.J.Davies (2008).
Structural and biochemical evidence for a boat-like transition state in beta-mannosidases.
  Nat Chem Biol, 4, 306-312.
PDB codes: 2vjx 2vl4 2vmf 2vo5 2vot 2vqt 2vqu 2vr4
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 codes are shown on the right.