The 10-megadalton pyruvate dehydrogenase complex contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3) and catalyzes the overall oxidative decarboxylation of pyruvate to form acetyl-CoA and CO(2) (PubMed:33567276, PubMed:34836937). E3BP is responsible for tethering E3 in proximity to the core, forming the entire metabolon, and the number of E3s is limited by the number of E3BPs (PubMed:34836937). Within the complex, pyruvate and thiamine pyrophosphate (TPP or vitamin B1) are bound by pyruvate dehydrogenase E1 subunits alpha and beta and pyruvate is decarboxylated leading to the 2-carbon hydrohyethyl bound to TPP. The E2 component contains covalently-bound lipoyl cofactors and transfers the hydroxyethyl group from TPP to an oxidized form of covalently bound lipoamide, and the resulting acetyl group is then transferred to free coenzyme A to form acetyl-CoA and reduced dihydrolipoamide-E2. Finally, the flavoprotein dihydrolipoamide dehydrogenase (E3) re-oxidizes the lipoyl group of dihydrolipoamide-E2 to form lipoamide-E2 and NADH. A fourth subunit, E3BP, is responsible for tethering E3 in proximity to the core, forming the entire metabolon (Probable). Eukaryotic pyruvate dehydrogenase (PDH) complexes are organized as a core consisting of the oligomeric dihydrolipoamide acetyl-transferase (E2), around which are arranged multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide dehydrogenase (E3) and protein X (E3BP) bound by non-covalent bonds (PubMed:33567276). The Chaetomium thermophilum PDH complex contains 60 E2 units, 12 E3BP units, about 20 E1 units, and 12 or more E3 units (PubMed:33567276). The units are organized in 1 E2 60-mer, 4 E3BP trimers, about 20 E1 tetramers, and a maximum of 12 E3 dimers (PubMed:33567276). The E3BP trimers are bound inside the icosahedral core with tetrahedral symmetry (PubMed:33567276). The sequence organization of E3BP is highly similar to E2, having an N-terminal lipoyl-binding domain (LD), a central peripheral subunit binding domain (PSBD), and the C-terminal core region connected by disordered linkers. E3BP is bound in a tripod-like manner and the interaction to the E2 core is primarily mediated by a loop region of E3BP (residues Pro-317 to Leu-336). Belongs to the 2-oxoacid dehydrogenase family.