Functional conformations for pyruvate carboxylase during catalysis explored by cryoelectron microscopy

Gorka Lasso, Linda P.C. Yu, David Gil, Melisa Lázaro, Liang Tong, Mikel Valle

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Summary The tetrameric enzyme pyruvate carboxylase (PC), a biotin-dependent carboxylase, produces oxaloacetate by two consecutive reactions that take place in distant active sites. Previous crystal structures revealed two different configurations for PC tetramers, the so-called symmetric and asymmetric, which were understood as characteristic molecular architectures for PC from different organisms. We have analyzed PC samples from Staphylococcus aureus while the enzyme generates oxaloacetate, expecting PC tetramers to display the conformational landscape relevant for its functioning. Using cryoelectron microscopy (cryo-EM) and sorting techniques, we detect previously defined symmetric and asymmetric architectures, demonstrating that PC maps both arrangements by large conformational changes. Furthermore, we observe that each configuration is coupled to one of the two consecutive enzymatic reactions. The findings describe the structural transitions relevant for the allosteric control of the multifunctional PC and demonstrate that by cryo-EM and classification, we can characterize freely working macromolecules.

Original languageEnglish (US)
Pages (from-to)911-922
Number of pages12
Issue number6
StatePublished - Jun 10 2014
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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