title: Molecular biology of the human pyruvate dehydrogenase complex: structural aspects of the E2 and E3 components.
abstract: The availability of the primary amino acid sequences of the E2 of PDC, alpha-KGDC and BCKADC from several prokaryotic and eukaryotic species has allowed us to compare the structural aspects of human PDC-E2 with those of the E2 components from the other complexes. The PDC-E2 components from all the species examined so far contain three structurally identifiable regions: the lipoyl-bearing domain, the E3-binding site, and the catalytic domain. The primary structure of the lipoyl-bearing domain shows considerable variation in its size, ranging from one to three repeating units of approximately 110 amino acids, but essentially preserving its function in the E2 components. In contrast, the sizes of the E3-binding site and the catalytic domain of PDC-E2 from several species are essentially similar and show considerable conservation of specific amino acid residues. Obviously, additional studies are warranted to better understand the structure-function relationships of these domains and the evolutionary conservation of PDC-E2 in different species. Similarly, the availability of the primary amino acid sequences of E3 from several prokaryotes and eukaryotes has also permitted comparison of the structural domains of these proteins with that of the known structure of human GR, a flavoprotein member of the pyridine nucleotide-disulfide oxidoreductase family. Four structural domains (FAD, NAD+, central, and interface domains) have been identified in the E3 components. On the basis of the comparison of the secondary structural elements of GR and E3, the core structure of these two proteins are shown to be similar. It is hoped that further analysis of E3 using site-directed mutagenesis and determination of its crystal structure will provide better insight into its structure-function relationships.
authors: Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
authors: T J
authors: TJ
authors: Thekkumkara
authors: G
authors: G
authors: Pons
authors: S
authors: S
authors: Mitroo
authors: J E
authors: JE
authors: Jentoft
authors: M S
authors: MS
authors: Patel
mesh_terms: D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D006801:Humans; D008099:Liver / Q000201:enzymology; D046911:Macromolecular Substances; D008961:Models, Structural; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
chemical_list: D046911:Macromolecular Substances; D011768:Pyruvate Dehydrogenase Complex; D012333:RNA, Messenger; D012313:RNA; D004247:DNA