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PDBsum entry 2cet
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Contents |
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Beta-glucosidase from thermotoga maritima in complex with phenethyl- substituted glucoimidazole
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Structure:
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Beta-glucosidase a. Chain: a, b. Synonym: gentiobiase, cellobiase, beta-d-glucoside glucohydrolase. Engineered: yes
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Source:
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Thermotoga maritima. Organism_taxid: 2336. Expressed in: escherichia coli. Expression_system_taxid: 511693.
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Resolution:
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1.97Å
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R-factor:
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0.195
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R-free:
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0.244
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Authors:
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T.M.Gloster,S.Roberts,A.Vasella,G.J.Davies
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Key ref:
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T.M.Gloster
et al.
(2006).
Structural, kinetic, and thermodynamic analysis of glucoimidazole-derived glycosidase inhibitors.
Biochemistry,
45,
11879-11884.
PubMed id:
DOI:
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Date:
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10-Feb-06
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Release date:
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27-Sep-06
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PROCHECK
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Headers
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References
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Q08638
(BGLA_THEMA) -
Beta-glucosidase A from Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8)
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Seq:
Struc:
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446 a.a.
435 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.3.2.1.21
- beta-glucosidase.
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Reaction:
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Hydrolysis of terminal, non-reducing beta-D-glucose residues with release of beta-D-glucose.
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DOI no:
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Biochemistry
45:11879-11884
(2006)
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PubMed id:
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Structural, kinetic, and thermodynamic analysis of glucoimidazole-derived glycosidase inhibitors.
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T.M.Gloster,
S.Roberts,
G.Perugino,
M.Rossi,
M.Moracci,
N.Panday,
M.Terinek,
A.Vasella,
G.J.Davies.
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ABSTRACT
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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.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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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.
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J Comput Chem,
32,
463-482.
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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.
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J Mol Model,
17,
443-464.
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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.
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BMC Biochem,
12,
11.
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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.
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Bioorg Med Chem,
19,
2136-2144.
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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.
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Appl Microbiol Biotechnol,
87,
9.
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J.R.Ketudat Cairns,
and
A.Esen
(2010).
β-Glucosidases.
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Cell Mol Life Sci,
67,
3389-3405.
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T.M.Gloster,
and
G.J.Davies
(2010).
Glycosidase inhibition: assessing mimicry of the transition state.
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Org Biomol Chem,
8,
305-320.
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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.
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Protein Sci,
18,
1541-1551.
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PDB codes:
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A.D.Hill,
and
P.J.Reilly
(2008).
Computational analysis of glycoside hydrolase family 1 specificities.
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Biopolymers,
89,
1021-1031.
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D.J.Vocadlo,
and
G.J.Davies
(2008).
Mechanistic insights into glycosidase chemistry.
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Curr Opin Chem Biol,
12,
539-555.
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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.
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Nat Chem Biol,
4,
306-312.
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PDB codes:
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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.
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Links
