Dihydrolipoamide dehydrogenase
From Proteopedia
GeneralDihyrolipoamide dehydrogenase (E3) is a part of the multienzyme complex of pyruvate dehydrogenase. This multienzyme complex catalyzes the formation of Acetyl-CoA from pyruvate via oxidative decarboxylation. E3 is a flavoprotein and contains FAD. See also 2-Oxoglutarate Dehydrogenase StructureIn E. coli this complex exists as 24 E2 proteins arranged in a cube, surrounded by 12 E1 proteins and 12 E3 proteins. Dihydrolipoamide dehydrogenase (E3) binds to the pyruvate dehydrogenase complex (and the center of the cube of E2 proteins) through a .‘[1]’ The E3 binding protein is a completely separate protein from E3, but serves to connect the E3 polypeptides to the overarching structure. The active site includes an FAD group, as well as forming a disulfide bond. When the substrate is not present, “covers” the catalytic site from being exposed to solvents. Dihydrolipoamide dehydrogenase (E3) is a SCOP alpha and beta (a/b) class protein of the FAD/NAD(P)-binding domain fold. MechanismThe redox reaction occurs through the influence of , between which there is a disulfide bond within a distorted alpha helix. This redox active disulfide bond becomes reduced in order to reoxidize the E2 enzyme of the multienzyme complex.‘[2]’ E2 donates protons and electrons to E3 in order to complete its catalytic cycle. The E3 enzyme’s flavin ring (FAD) funnels electrons from the disulfide bond to itself, , reoxidizing the E3, and leaving it ready for the beginning of its catalytic cycle again. DiseaseDLD deficiency is a rare metabolic disorder causing neurological or liver impairment[3]. RegulationThe regulation of Dihidrolipoamide dehydrogenase (E3) kinetically comes through regulation of the entire Pyruvate Dehydrogenase complex. As would be expected, one of the main regulators is the presence of its product, acetyl-CoA as well as NADH. This is through the E1 reaction of the complex, but necessarily effects the E3 reaction. However, the E1 portion of the complex is also regulated by phosphatase and kinase in phosphorylation and dephosphorylation reactions.‘[4]’ 3D structures of dihydrolipoamide dehydrogenaseUpdated on 06-April-2025
References
| ||||||||||||
Proteopedia Page Contributors and Editors (what is this?)
Michal Harel, Nicholas Rockefeller, Alexander Berchansky, David Canner, Shane Michael Evans, Jaime Prilusky
