title: The three-dimensional structure of the biotin carboxylase-biotin carboxyl carrier protein complex of E. coli acetyl-CoA carboxylase.
abstract: Acetyl-coenzyme A (acetyl-CoA) carboxylase is a biotin-dependent, multifunctional enzyme that catalyzes the regulated step in fatty acid synthesis. The Escherichia coli enzyme is composed of a homodimeric biotin carboxylase (BC), biotinylated biotin carboxyl carrier protein (BCCP), and an α2β2 heterotetrameric carboxyltransferase. This enzyme complex catalyzes two half-reactions to form malonyl-coenzyme A. BC and BCCP participate in the first half-reaction, whereas carboxyltransferase and BCCP are involved in the second. Three-dimensional structures have been reported for the individual subunits; however, the structural basis for how BCCP reacts with the carboxylase or transferase is unknown. Therefore, we report here the crystal structure of E. coli BCCP complexed with BC to a resolution of 2.49 Å. The protein-protein complex shows a unique quaternary structure and two distinct interfaces for each BCCP monomer. These BCCP binding sites are unique compared to phylogenetically related biotin-dependent carboxylases and therefore provide novel targets for developing antibiotics against bacterial acetyl-CoA carboxylase.
authors.affiliation: Division of Biochemistry and Molecular Biology, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Tyler C
authors.initials: TC
authors.lastname: Broussard
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Kobe
authors.forename: Svetlana
authors.initials: S
authors.lastname: Pakhomova
authors.forename: David B
authors.initials: DB
authors.lastname: Neau
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Price
authors.forename: Tyler S
authors.initials: TS
authors.lastname: Champion
authors.forename: Grover L
authors.initials: GL
authors.lastname: Waldrop
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000737:chemistry*; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry*; D003460:Crystallization; D004926:Escherichia coli / Q000201:enzymology*; D054889:Fatty Acid Synthase, Type II / Q000737:chemistry; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry*; D011487:Protein Conformation; D014961:X-Ray Diffraction
chemical_list: D046912:Multiprotein Complexes; D054889:Fatty Acid Synthase, Type II; D019731:Carbon-Nitrogen Ligases; C019791:biotin carboxylase; D000103:Acetyl-CoA Carboxylase; C079633:biotin carboxyl carrier protein