The Three-Dimensional Structure of the Biotin Carboxylase-Biotin Carboxyl Carrier Protein Complex of E. coli Acetyl-CoA Carboxylase

• Published in: Structure (London) 2013-04, Vol.21 (4), p.650-657
• Main Authors: Broussard, Tyler C., Kobe, Matthew J., Pakhomova, Svetlana, Neau, David B., Price, Amanda E., Champion, Tyler S., Waldrop, Grover L.
• Format: Article
• Language: English
• Subjects: Acetyl-CoA Carboxylase - chemistry; Bacteria; Biotin; Carbon-Nitrogen Ligases - chemistry; Carriers; Crystallization; Enzymes; Escherichia coli; Escherichia coli - enzymology; Fatty Acid Synthase, Type II - chemistry; Fatty acids; Models, Molecular; Multiprotein Complexes - chemistry; Protein Conformation; Proteins; Three dimensional; X-Ray Diffraction
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2013.02.001

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. ► Biotin carboxyl carrier protein-biotin carboxylase (BCCP-BC) forms a hetero-octamer ► The BCCP-BC structure is a complex of acetyl-CoA carboxylase ► The BCCP-BC complex provides insight into the mechanism of biotinylation in vivo ► BCCP-BC complex interfaces reveal potential targets for novel antibiotic development Broussard et al. describe the structure of biotin carboxylase-biotin carboxyl carrier protein complex from E. coli. These two proteins are part of the multifunctional enzyme acetyl-CoA carboxylase, which catalyzes the first committed step in fatty acid synthesis, and thus a potential drug target.