Details

Autor(en) / Beteiligte

• Broussard, Tyler C.
• Kobe, Matthew J.
• Pakhomova, Svetlana
• Neau, David B.
• Price, Amanda E.
• Champion, Tyler S.
• Waldrop, Grover L.

Titel

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

Ist Teil von

• Structure (London), 2013-04, Vol.21 (4), p.650-657

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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.