Aldose-6-phosphate reductase from apple leaves: Importance of the quaternary structure for enzyme activity
摘要:
Aldose-6-phosphate reductase (A6PRase) is a key enzyme for glucitol biosynthesis in plants from the Rosaceae family. To gain on molecular tools for enzymological studies, we developed an accurate system for the heterologous expression of A6PRase from apple leaves. The recombinant enzyme was expressed with a His-tag alternatively placed in the N- or C-terminus, thus allowing the one-step protein purification by immobilized metal affinity chromatography. Both, the N- and the C-term tagged enzymes exhibited similar affinity toward substrates, although the k(cat) of the latter enzyme was 80-fold lower than that having the His-tag in the N-term. Gel filtration chromatography showed different oligomeric structures arranged by the N- (dimer) and the C-term (monomer) tagged enzymes. These results, reinforced by homology modeling studies, point out the relevance of the C-term domain in the structure of A6PRase to conform an enzyme having optimal specific activity and the proper quaternary structure. (C) 2009 Elsevier Masson SAS. All rights reserved.
[EN] SULFONYL COMPOUNDS THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN<br/>[FR] COMPOSÉS DE SULFONYLE QUI INTERAGISSENT AVEC LA PROTÉINE RÉGULATRICE DE LA GLUCOKINASE
申请人:AMGEN INC
公开号:WO2013123444A1
公开(公告)日:2013-08-22
The present invention relates to sulfonyl compounds that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.
Para-aryl or heterocyclic substituted phenyl glucokinase activators
申请人:——
公开号:US20020002190A1
公开(公告)日:2002-01-03
Para-aryl or heteroaryl substituted phenyl amides which are active as glucokinase activators to increase insulin secretion which makes them useful for treating type II diabetes.
2,3-Di-substituted N-heteroaromatic propionamides with said substitution at the 2-position being a substituted phenyl group and at the 3-position being a cycloalkyl ring, said propionamides being glucokinase activators which increase insulin secretion in the treatment of type II diabetes.
Provided herein are compounds of the formula (I):
as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of metabolic diseases and disorders such as, for example, type II diabetes mellitus.
[EN] SULFONYLPIPERAZINE DERIVATIVES THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN FOR THE TREATMENT OF DIABETES<br/>[FR] DÉRIVÉS DE SULFONYLPIPÉRAZINE QUI INTERAGISSENT AVEC LA PROTÉINE RÉGULATRICE DE LA GLUCOKINASE POUR LE TRAITEMENT DU DIABÈTE
申请人:AMGEN INC
公开号:WO2012027261A1
公开(公告)日:2012-03-01
The present invention relates to compounds of Formula I, or pharmaceutically acceptable salts thereof, that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.