title: The enzymes of biotin dependent CO₂ metabolism: what structures reveal about their reaction mechanisms.
abstract: Biotin is the major cofactor involved in carbon dioxide metabolism. Indeed, biotin-dependent enzymes are ubiquitous in nature and are involved in a myriad of metabolic processes including fatty acid synthesis and gluconeogenesis. The cofactor, itself, is composed of a ureido ring, a tetrahydrothiophene ring, and a valeric acid side chain. It is the ureido ring that functions as the CO₂ carrier. A complete understanding of biotin-dependent enzymes is critically important for translational research in light of the fact that some of these enzymes serve as targets for anti-obesity agents, antibiotics, and herbicides. Prior to 1990, however, there was a dearth of information regarding the molecular architectures of biotin-dependent enzymes. In recent years there has been an explosion in the number of three-dimensional structures reported for these proteins. Here we review our current understanding of the structures and functions of biotin-dependent enzymes. In addition, we provide a critical analysis of what these structures have and have not revealed about biotin-dependent catalysis.
authors.affiliation: Division of Biochemistry and Molecular Biology, Louisiana State University, Baton Rouge, Louisiana 70803, USA. gwaldro@lsu.edu
authors.forename: Grover L
authors.initials: GL
authors.lastname: Waldrop
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Holden
authors.forename: Martin
authors.initials: M
authors.lastname: St Maurice
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D001710:Biotin / Q000737:chemistry / Q000378:metabolism*; D002245:Carbon Dioxide / Q000737:chemistry / Q000378:metabolism*; D002262:Carboxy-Lyases / Q000737:chemistry / Q000378:metabolism*; D019878:Carboxyl and Carbamoyl Transferases / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D002245:Carbon Dioxide; D001710:Biotin; D000255:Adenosine Triphosphate; D019878:Carboxyl and Carbamoyl Transferases; D002262:Carboxy-Lyases