3HO8

Crystal Structure of S. aureus Pyruvate Carboxylase in complex with Coenzyme A

Summary for 3HO8

• Entry DOI: 10.2210/pdb3ho8/pdb
• Descriptor: Pyruvate carboxylase, COENZYME A, MANGANESE (II) ION, ... (4 entities in total)
• Functional Keywords: tim barrel, pyruvate, ligase
• Biological source: Staphylococcus aureus subsp. aureus Mu50
• Total number of polymer chains: 4
• Total formula weight: 518576.17

Authors

Tong, L.,Yu, L.P.C. (deposition date: 2009-06-01, release date: 2009-06-30, Last modification date: 2024-02-21)

Primary citation

Yu, L.P.,Xiang, S.,Lasso, G.,Gil, D.,Valle, M.,Tong, L.
A Symmetrical Tetramer for S. aureus Pyruvate Carboxylase in Complex with Coenzyme A.
Structure, 17:823-832, 2009

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.

PubMed: 19523900
DOI: 10.1016/j.str.2009.04.008

Experimental method

X-RAY DIFFRACTION (2.9 Å)