Crystal Structures of Human and Staphylococcus aureus Pyruvate Carboxylase and Molecular Insights into the Carboxyltransfer Reaction

Journal Article · Tue Jan 01 04:00:00 EST 2008 · Nature Structural and Molecular Biology

DOI:https://doi.org/10.1038/nsmb.1393· OSTI ID:959845

Xiang, S; Tong, L

Pyruvate carboxylase (PC) catalyzes the biotin-dependent production of oxaloacetate and has important roles in gluconeogenesis, lipogenesis, insulin secretion and other cellular processes. PC contains the biotin carboxylase (BC), carboxyltransferase (CT) and biotin-carboxyl carrier protein (BCCP) domains. We report here the crystal structures at 2.8-Angstroms resolution of full-length PC from Staphylococcus aureus and the C-terminal region (missing only the BC domain) of human PC. A conserved tetrameric association is observed for both enzymes, and our structural and mutagenesis studies reveal a previously uncharacterized domain, the PC tetramerization (PT) domain, which is important for oligomerization. A BCCP domain is located in the active site of the CT domain, providing the first molecular insights into how biotin participates in the carboxyltransfer reaction. There are dramatic differences in domain positions in the monomer and the organization of the tetramer between these enzymes and the PC from Rhizobium etli.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 959845
• Report Number(s): BNL--82831-2009-JA
• Journal Information: Nature Structural and Molecular Biology, Journal Name: Nature Structural and Molecular Biology Journal Issue: 3 Vol. 15
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
BIOTIN
CARBOXYLASE
CRYSTAL STRUCTURE
ENZYMES
INSULIN
MONOMERS
MUTAGENESIS
PRODUCTION
PROTEINS
RESOLUTION
RHIZOBIUM
SECRETION
STAPHYLOCOCCUS
national synchrotron light source