PDBsum entry 1oin

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Hydrolase PDB id
Protein chains
442 a.a. *
G2F ×2
Waters ×413
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Family 1 b-glucosidase from thermotoga maritima
Structure: Beta-glucosidase a. Chain: a, b. Synonym: gentiobiase, cellobiase, beta-d-glucoside glucohyd engineered: yes
Source: Thermotoga maritima. Organism_taxid: 2336. Expressed in: escherichia coli. Expression_system_taxid: 511693.
2.15Å     R-factor:   0.204     R-free:   0.256
Authors: T.Gloster,D.L.Zechel,A.B.Boraston,C.M.Boraston,J.M.Macdonald D.M.Tilbrook,R.V.Stick,G.J.Davies
Key ref: D.L.Zechel et al. (2003). Iminosugar glycosidase inhibitors: structural and thermodynamic dissection of the binding of isofagomine and 1-deoxynojirimycin to beta-glucosidases. J Am Chem Soc, 125, 14313-14323. PubMed id: 14624580 DOI: 10.1021/ja036833h
19-Jun-03     Release date:   25-Nov-03    
Go to PROCHECK summary

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

 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!
  Biological process     metabolic process   4 terms 
  Biochemical function     hydrolase activity     4 terms  


DOI no: 10.1021/ja036833h J Am Chem Soc 125:14313-14323 (2003)
PubMed id: 14624580  
Iminosugar glycosidase inhibitors: structural and thermodynamic dissection of the binding of isofagomine and 1-deoxynojirimycin to beta-glucosidases.
D.L.Zechel, A.B.Boraston, T.Gloster, C.M.Boraston, J.M.Macdonald, D.M.Tilbrook, R.V.Stick, G.J.Davies.
The design and synthesis of transition-state mimics reflects the growing need both to understand enzymatic catalysis and to influence strategies for therapeutic intervention. Iminosugars are among the most potent inhibitors of glycosidases. Here, the binding of 1-deoxynojirimycin and (+)-isofagomine to the "family GH-1" beta-glucosidase of Thermotoga maritima is investigated by kinetic analysis, isothermal titration calorimetry, and X-ray crystallography. The binding of both of these iminosugar inhibitors is driven by a large and favorable enthalpy. The greater inhibitory power of isofagomine, relative to 1-deoxynojirimycin, however, resides in its significantly more favorable entropy; indeed the differing thermodynamic signatures of these inhibitors are further highlighted by the markedly different heat capacity values for binding. The pH dependence of catalysis and of inhibition suggests that the inhibitory species are protonated inhibitors bound to enzymes whose acid/base and nucleophile are ionized, while calorimetry indicates that one proton is released from the enzyme upon binding at the pH optimum of catalysis (pH 5.8). Given that these results contradict earlier proposals that the binding of racemic isofagomine to sweet almond beta-glucosidase was entropically driven (Bülow, A. et al. J. Am. Chem. Soc. 2000, 122, 8567-8568), we reinvestigated the binding of 1-deoxynojirimycin and isofagomine to the sweet almond enzyme. Calorimetry confirms that the binding of isofagomine to sweet almond beta-glucosidases is, as observed for the T. maritima enzyme, driven by a large favorable enthalpy. The crystallographic structures of the native T. maritima beta-glucosidase, and its complexes with isofagomine and 1-deoxynojirimycin, all at approximately 2.1 A resolution, reveal that additional ordering of bound solvent may present an entropic penalty to 1-deoxynojirimycin binding that does not penalize isofagomine.

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.  
20665773 A.Lammerts van Bueren, S.D.Popat, C.H.Lin, and G.J.Davies (2010).
Structural and thermodynamic analyses of α-L-fucosidase inhibitors.
  Chembiochem, 11, 1971-1974.
PDB codes: 2xib 2xii
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).
  Cell Mol Life Sci, 67, 3389-3405.  
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.  
19532990 M.Aguilar-Moncayo, T.M.Gloster, J.P.Turkenburg, M.I.García-Moreno, C.Ortiz Mellet, G.J.Davies, and J.M.García Fernández (2009).
Glycosidase inhibition by ring-modified castanospermine analogues: tackling enzyme selectivity by inhibitor tailoring.
  Org Biomol Chem, 7, 2738-2747.
PDB codes: 2wbg 2wc3 2wc4
18074341 A.D.Hill, and P.J.Reilly (2008).
A Gibbs free energy correlation for automated docking of carbohydrates.
  J Comput Chem, 29, 1131-1141.  
18615662 A.D.Hill, and P.J.Reilly (2008).
Computational analysis of glycoside hydrolase family 1 specificities.
  Biopolymers, 89, 1021-1031.  
18256510 H.Saino, M.Mizutani, J.Hiratake, and K.Sakata (2008).
Expression and biochemical characterization of beta-primeverosidase and application of beta-primeverosylamidine to affinity purification.
  Biosci Biotechnol Biochem, 72, 376-383.  
18712828 K.H.Nam, S.J.Kim, M.Y.Kim, J.H.Kim, Y.S.Yeo, C.M.Lee, H.K.Jun, and K.Y.Hwang (2008).
Crystal structure of engineered beta-glucosidase from a soil metagenome.
  Proteins, 73, 788-793.
PDB code: 3cmj
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
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.  
18023045 T.Tsukada, K.Igarashi, S.Fushinobu, and M.Samejima (2008).
Role of subsite +1 residues in pH dependence and catalytic activity of the glycoside hydrolase family 1 beta-glucosidase BGL1A from the basidiomycete Phanerochaete chrysosporium.
  Biotechnol Bioeng, 99, 1295-1302.  
17373018 H.M.Chen, and S.G.Withers (2007).
Facile synthesis of 2,4-dinitrophenyl alpha-D-glycopyranosides as chromogenic substrates for alpha-glycosidases.
  Chembiochem, 8, 719-722.  
17503162 M.León, P.Isorna, M.Menéndez, J.Sanz-Aparicio, and J.Polaina (2007).
Comparative study and mutational analysis of distinctive structural elements of hyperthermophilic enzymes.
  Protein J, 26, 435-444.
PDB code: 1uwi
  17768360 P.Turner, A.Pramhed, E.Kanders, M.Hedström, E.N.Karlsson, and D.T.Logan (2007).
Expression, purification, crystallization and preliminary X-ray diffraction analysis of Thermotoga neapolitana beta-glucosidase B.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 802-806.  
17252125 T.M.Gloster, R.Madsen, and G.J.Davies (2007).
Structural basis for cyclophellitol inhibition of a beta-glucosidase.
  Org Biomol Chem, 5, 444-446.
PDB code: 2jal
16628756 T.M.Gloster, R.Madsen, and G.J.Davies (2006).
Dissection of conformationally restricted inhibitors binding to a beta-glucosidase.
  Chembiochem, 7, 738-742.
PDB codes: 2cbu 2cbv
15987675 E.J.Taylor, A.Goyal, C.I.Guerreiro, J.A.Prates, V.A.Money, N.Ferry, C.Morland, A.Planas, J.A.Macdonald, R.V.Stick, H.J.Gilbert, C.M.Fontes, and G.J.Davies (2005).
How family 26 glycoside hydrolases orchestrate catalysis on different polysaccharides: structure and activity of a Clostridium thermocellum lichenase, CtLic26A.
  J Biol Chem, 280, 32761-32767.
PDB codes: 2bv9 2bvd
15853815 J.Jänis, J.Hakanpää, N.Hakulinen, F.M.Ibatullin, A.Hoxha, P.J.Derrick, J.Rouvinen, and P.Vainiotalo (2005).
Determination of thioxylo-oligosaccharide binding to family 11 xylanases using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry and X-ray crystallography.
  FEBS J, 272, 2317-2333.
PDB code: 1xnk
16356852 L.Dolecková-Maresová, M.Pavlík, M.Horn, and M.Mares (2005).
De novo design of alpha-amylase inhibitor: a small linear mimetic of macromolecular proteinaceous ligands.
  Chem Biol, 12, 1349-1357.  
16082555 T.H.Park, K.W.Choi, C.S.Park, S.B.Lee, H.Y.Kang, K.J.Shon, J.S.Park, and J.Cha (2005).
Substrate specificity and transglycosylation catalyzed by a thermostable beta-glucosidase from marine hyperthermophile Thermotoga neapolitana.
  Appl Microbiol Biotechnol, 69, 411-422.  
15515081 F.Vincent, T.M.Gloster, J.Macdonald, C.Morland, R.V.Stick, F.M.Dias, J.A.Prates, C.M.Fontes, H.J.Gilbert, and G.J.Davies (2004).
Common inhibition of both beta-glucosidases and beta-mannosidases by isofagomine lactam reflects different conformational itineraries for pyranoside hydrolysis.
  Chembiochem, 5, 1596-1599.
PDB codes: 1uz1 1uz4
15384176 M.J.Cliff, A.Gutierrez, and J.E.Ladbury (2004).
A survey of the year 2003 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 17, 513-523.  
15356002 T.M.Gloster, J.M.Macdonald, C.A.Tarling, R.V.Stick, S.G.Withers, and G.J.Davies (2004).
Structural, thermodynamic, and kinetic analyses of tetrahydrooxazine-derived inhibitors bound to beta-glucosidases.
  J Biol Chem, 279, 49236-49242.
PDB codes: 1w3j 1w3k 1w3l
15252054 Y.W.Kim, S.S.Lee, R.A.Warren, and S.G.Withers (2004).
Directed evolution of a glycosynthase from Agrobacterium sp. increases its catalytic activity dramatically and expands its substrate repertoire.
  J Biol Chem, 279, 42787-42793.  
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.