Figure 1.

Schematic representation of the proposed mechanism of 2-oxoglutarate dehydrogenase complex (OGDHC). (A) It consists of three component enzymes: oxoglutarate dehydrogenase (E1), dihydro-lipoamide succinyltransferase (E2), and dihydro-lipoamide dehydrogenase (E3). The schematic representation here does not describe true stoichiometry of the multiple copies of three enzymes in the complex. The binding domain and lipoyl domain of E2 polypeptide are connected to the complex core with flexible links (dotted lines), are used here to describe the mechanism in which a single lipoic acid rotates between the three catalytic sites. In the catalytic cycle, the disulfide at the tip of the lipoyl can be in oxidized, reduced or semi-reduced lipoate forms, the later one is connected with succinyl residue transferred from oxoglutarate. (B) This schematic illustrates the proposed kinetic schemes along with the mechanism of conformational changes. The forward reaction is read in the clockwise direction. The complex has three binding sites: one for each composite enzyme. E1 binds to 2-oxoglutarate or corresponding product CO2 (top), E2 binds to COA or corresponding product Succinyl-CoA (bottom-right), E3 binds to NAD or corresponding product NADH (bottom-left). It is assumed that, in the process of conformational changes, the rotation of one lipoic acid between three catalytic sites leads to transfer succinyl from E1 to E2 and proton from E2 to E3.

Qi et al. BMC Biochemistry 2011 12:53   doi:10.1186/1471-2091-12-53
Download authors' original image