2cet: Difference between revisions
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==Overview== | ==Overview== | ||
Inhibition of glycosidases has great potential in the quest for highly | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Thermotoga maritima]] | [[Category: Thermotoga maritima]] | ||
[[Category: Davies, G | [[Category: Davies, G J.]] | ||
[[Category: Gloster, T | [[Category: Gloster, T M.]] | ||
[[Category: Roberts, S.]] | [[Category: Roberts, S.]] | ||
[[Category: Vasella, A.]] | [[Category: Vasella, A.]] | ||
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[[Category: transition state mimic]] | [[Category: transition state mimic]] | ||
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Revision as of 17:47, 21 February 2008
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BETA-GLUCOSIDASE FROM THERMOTOGA MARITIMA IN COMPLEX WITH PHENETHYL-SUBSTITUTED GLUCOIMIDAZOLE
OverviewOverview
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.
About this StructureAbout this Structure
2CET is a Single protein structure of sequence from Thermotoga maritima with , and as ligands. Active as Beta-glucosidase, with EC number 3.2.1.21 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Structural, kinetic, and thermodynamic analysis of glucoimidazole-derived glycosidase inhibitors., Gloster TM, Roberts S, Perugino G, Rossi M, Moracci M, Panday N, Terinek M, Vasella A, Davies GJ, Biochemistry. 2006 Oct 3;45(39):11879-84. PMID:17002288
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