title: The anatomy of transcarboxylase and the role of its subunits.
abstract: Biotin enzymes in general catalyze the fixation of CO2 and in a few instances decarboxylations yielding CO2. Transcarboxylase is an exception; it catalyzes the transfer of a carboxyl group from one compound to another and CO2 is not involved. This enzyme plays an essential role in the formation of propionic acid by propionibacteria and its structure and catalytic mechanism have been extensively investigated including studies of the quaternary structure by electron microscopy. The structure is complex, consisting of three types of subunits: (1) a central hexameric subunit, (2) six dimeric outside subunits, and (3) twelve biotinyl subunits which bind the outside subunits to the central subunit. There are 12 substrate sites on the central subunit (2 per polypeptide) and 2 substrate sites on each of the dimeric outside subunits. The carboxyl is transferred between these sites via the biotin of the biotinyl subunit. The biotinyl subunit (approximately 123 residues) has been completely sequenced and it has been shown that the first 42 residues serve in binding the outside subunits to the central subunit and the remainder of the sequence is involved in placing the biotin between the subunits so that it may serve as the carboxyl carrier between the substrate sites on the central and outside subunits. It is proposed that the dual sites on the polypeptides of the central subunit have arisen as a consequence of gene duplication and fusion. An intriguing question is why such a complicated structure is required for catalysis of a rather simple reaction.
mesh_terms: D000595:Amino Acid Sequence; D001710:Biotin / Q000378:metabolism; D046911:Macromolecular Substances; D008764:Methylmalonic Acid / Q000031:analogs & derivatives; D008958:Models, Molecular; D011487:Protein Conformation; D014166:Transferases / Q000378:metabolism*; D014357:Trypsin / Q000494:pharmacology
chemical_list: D046911:Macromolecular Substances; D001710:Biotin; D008764:Methylmalonic Acid; D014166:Transferases; D014357:Trypsin