Institute of Organic and Pharmaceutical Chemistry
The National Hellenic Research Foundation
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Phosphoenolpyruvate caroxykinase
Phosphoenolpyruvate carboxykinase (PEPCK) catalyses the decarboxylation and mononucleoside triphosphate-dependent phosphorylation of oxaloacetate to form phosphoenolpyruvate and nucleoside diphospate. PEPCK is a central enzyme in carbohydrate metabolism that helps to regulate blood glucose levels in mammals. Transgenic mice overexpressing PEPCK showed unsuppressed liver glucose production and developed type 2 diabetes. PEPCK has therefore been suggested as a potential drug target in the treatment of this disease. The project is aiming to the crystallisation of human recombinant PEPCK, and initiation of crystallographic studies on structure determination of PEPCK in complex with inhibitors of the enzyme such as 3-mercaptopicolinic acid and oxalic acid. Detailed analyses of complex structures and mapping of the molecular interactions should provide rationalisations for the affinities of these compounds that might give rise to better inhibitors, potential drugs for controlling hyperglycaemia in type 2 diabetes
Research Interests:
Control of glycogen metabolism
Phosphoenolpyruvate carboxykinase
Carbohydrate
recognition
Human TAFs9 proteins
Xylanases and feruloyl esterases