title: Molecular architecture of the pyruvate dehydrogenase complex: bridging the gap.
abstract: The PDC (pyruvate dehydrogenase complex) is a high-molecular-mass (4-11 MDa) complex of critical importance for glucose homoeostasis in mammals. Its multi-enzyme structure allows for substrate channelling and active-site coupling: sequential catalytic reactions proceed through the rapid transfer of intermediates between individual components and without diffusion into the bulk medium due to its 'swinging arm' that is able to visit all PDC active sites. Optimal positioning of individual components within this multi-subunit complex further affects the efficiency of the overall reaction and stability of its intermediates. Mammalian PDC comprises a 60-meric pentagonal dodecahedral dihydrolipoamide (E2) core attached to which are 30 pyruvate decarboxylase (E1) heterotetramers and six dihydrolipoamide (E3) homodimers at maximal occupancy. Stable E3 integration is mediated by an accessory E3-binding protein associated with the E2 core. Association of the peripheral E1 and E3 enzymes with the PDC core has been studied intensively in recent years and has yielded some interesting and substantial differences when compared with prokaryotic PDCs.
authors.affiliation: Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK. m.smolle.1@research.gla.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Smolle
authors.forename: J G
authors.initials: JG
authors.lastname: Lindsay
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D021122:Protein Subunits; D011768:Pyruvate Dehydrogenase Complex