3bg3

From Proteopedia

Crystal Structure of Human Pyruvate Carboxylase (missing the biotin carboxylase domain at the N-terminus)

Structural highlights

3bg3 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PYC_HUMAN Defects in PC are the cause of pyruvate carboxylase deficiency (PC deficiency) [MIM:266150. PC deficiency leads to lactic acidosis, mental retardation and death. It occurs in three forms: mild or type A, severe neonatal or type B, and a very mild lacticacidemia.

Function

PYC_HUMAN Pyruvate carboxylase catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in the second. Catalyzes in a tissue specific manner, the initial reactions of glucose (liver, kidney) and lipid (adipose tissue, liver, brain) synthesis from pyruvate.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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-A 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.

Crystal structures of human and Staphylococcus aureus pyruvate carboxylase and molecular insights into the carboxyltransfer reaction.,Xiang S, Tong L Nat Struct Mol Biol. 2008 Mar;15(3):295-302. Epub 2008 Feb 24. PMID:18297087^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Xiang S, Tong L. Crystal structures of human and Staphylococcus aureus pyruvate carboxylase and molecular insights into the carboxyltransfer reaction. Nat Struct Mol Biol. 2008 Mar;15(3):295-302. Epub 2008 Feb 24. PMID:18297087 doi:10.1038/nsmb.1393