A symmetrical tetramer for S. aureus pyruvate carboxylase in complex with coenzyme A.

Article Details

Citation

Copy to clipboard

Yu LP, Xiang S, Lasso G, Gil D, Valle M, Tong L

A symmetrical tetramer for S. aureus pyruvate carboxylase in complex with coenzyme A.

Structure. 2009 Jun 10;17(6):823-32. doi: 10.1016/j.str.2009.04.008.

PubMed ID

19523900 [ View in PubMed

]

Abstract

Pyruvate carboxylase (PC) is a conserved metabolic enzyme with important cellular functions. We report crystallographic and cryo-electron microscopy (EM) studies of Staphylococcus aureus PC (SaPC) in complex with acetyl-CoA, an allosteric activator, and mutagenesis, biochemical, and structural studies of the biotin binding site of its carboxyltransferase (CT) domain. The disease-causing A610T mutation abolishes catalytic activity by blocking biotin binding to the CT active site, and Thr908 might play a catalytic role in the CT reaction. The crystal structure of SaPC in complex with CoA reveals a symmetrical tetramer, with one CoA molecule bound to each monomer, and cryo-EM studies confirm the symmetrical nature of the tetramer. These observations are in sharp contrast to the highly asymmetrical tetramer of Rhizobium etli PC in complex with ethyl-CoA. Our structural information suggests that acetyl-CoA promotes a conformation for the dimer of the biotin carboxylase domain of PC that might be catalytically more competent.

DrugBank Data that Cites this Article

Polypeptides

Name	UniProt ID
Pyruvate carboxylase	A0A0H3JRU9	Details