Dihydrolipoamide dehydrogenase

spinqualitylabelsall models FAD-containing dihydrolipoamide dehydrogenase complexed with NAD 1lvl Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D General Dihyrolipoamide 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 Structure In 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 coupling with E3 binding protein.‘’ 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 Cys 43 and Cys 48 forming a disulfide bond. When the substrate is not present, Tyr 181 “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. Mechanism The redox reaction occurs through the influence of Cys 43 and Cys 48, 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.‘’ 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, then binds to NAD+ and donates electrons, reoxidizing the E3, and leaving it ready for the beginning of its catalytic cycle again. Disease DLD deficiency is a rare metabolic disorder causing neurological or liver impairment. Regulation The 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.‘’ 3D structures of dihydrolipoamide dehydrogenase Updated on 06-April-2025 {"openlevels":0} DLD 2ihw – bDLD E2 - bovine 1ivi – DLD – pig 1dxl – DLD – pea 1jeh – yDLD E3 – yeast 1lpf – DLD – Pseudomonas fluorescens 3lad – DLD – Azotobacter vinelandii 3l60 – MtDLD E2 – Mycobacterium tuberculosis 2a8x - MtDLD E3 3l8k – DLD – Sulfolobus solfataricus 3urh – DLD – Sinorhizobium meliloti 1w4i – PaDLD peripheral-subunit binding domain – Pyrobaculum aerophilum - NMR 1w4j, 1w4k – PaDLD peripheral-subunit binding domain (mutant) - NMR 3ic9 – DLD – Colwellia psychrerythraea 2qae – DLD – Trypanosoma cruzi 2eq6 – TtDLD – Thermus thermophilus 2yqu – TtDLD E3 2eq7, 2eq8, 2eq9 – TtDLD E2+E3 DLD binary complexes 3rnm – hDLD subunit-binding domain + dihydrolipoyl dehydrogenase – human 2f5z, 1zy8 – hDLD E3 + pyruvate dehydrogenase E3-binding domain 1zmc, 1zmd – hDLD + NAD 6i4q – hDLD + FAD 5j5z, 6hg8, 6i4p, 6i4r, 6i4s, 6i4t, 6i4u, 6i4z, 7psc, 7zyt – hDLD (mutant) + FAD 2ii3, 2ii4, 2ii5 – bDLD + CoA 1v59 – yDLD + NAD 1lvl – PpDLD + NAD – Pseudomonas putida 6awa - PpDLD + FAD + AMP 3ii4 – MtDLD + inhibitor 4m52, 8u0q – MtDLD + FAD + sulfonamide inhibitor 8ct4 – MtDLD + FAD + sulfonamide inhibitor – Cryo EM 7kmy – MtDLD + FAD + pyridine inhibitor 1ebd – DLD + dihydrolipoamide acetyltransferase binding domain – Geobacillus stearothermophilus 4jdr – DLD + FAD – Escherichia coli 5u8u – DLD + FAD – Pseudomonas aeruginosa 5u25 – DLD + FAD – Neisseria gonorrhoeae 6aon – DLD + FAD – Bordetella pertussis 6cmz – DLD + FAD + NAD – Burkholderia cenocepacia 6uzi – DLD + FAD – Elizabethkingia anophelis<br /> 6bz0 – DLD + FAD – Acinetobacter baumannii 8ajj – DLD + FAD – Staphylococcus aureus<br />

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