A Symmetrical Tetramer for S. aureus Pyruvate Carboxylase in Complex with Coenzyme A

Linda P.C. Yu, Song Xiang, Gorka Lasso, David Gil, Mikel Valle, Liang Tong

Research output: Contribution to journalArticle

46 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)823-832
Number of pages10
JournalStructure
Volume17
Issue number6
DOIs
StatePublished - Jun 10 2009
Externally publishedYes

Keywords

  • PROTEINS

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'A Symmetrical Tetramer for S. aureus Pyruvate Carboxylase in Complex with Coenzyme A'. Together they form a unique fingerprint.

  • Cite this