2cet: Difference between revisions

Revision as of 21:57, 3 May 2008

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. 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 Page seeded by OCA on Sat May 3 21:57:50 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:2cet.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2cet |SIZE=350|CAPTION= <scene name='initialview01'>2cet</scene>, resolution 1.97&Aring;
+The line below this paragraph, containing "STRUCTURE_2cet", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=NUC:Pgi+Binding+Site+For+Chain+B'>NUC</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PGI:(5R,6R,7S,8S)-5-(HYDROXYMETHYL)-2-(2-PHENYLETHYL)-1,5,6,7,8,8A-HEXAHYDROIMIDAZO[1,2-A]PYRIDINE-6,7,8-TRIOL'>PGI</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-glucosidase Beta-glucosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.21 3.2.1.21] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_2cet|  PDB=2cet  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2cet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cet OCA], [http://www.ebi.ac.uk/pdbsum/2cet PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2cet RCSB]</span>
-}}
 '''BETA-GLUCOSIDASE FROM THERMOTOGA MARITIMA IN COMPLEX WITH PHENETHYL-SUBSTITUTED GLUCOIMIDAZOLE'''
@@ Line 30: / Line 27: @@
 [[Category: Roberts, S.]]
 [[Category: Vasella, A.]]
-[[Category: family 1]]
+[[Category: Family 1]]
-[[Category: glycoside hydrolase]]
+[[Category: Glycoside hydrolase]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: inhibitor]]
+[[Category: Inhibitor]]
-[[Category: phenethyl-substituted glucoimidazole]]
+[[Category: Phenethyl-substituted glucoimidazole]]
-[[Category: transition state mimic]]
+[[Category: Transition state mimic]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 21:57:50 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:20:30 2008''