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CryoEM structural exploration of catalytically active enzyme pyruvate carboxylase

Author

Listed:
  • Jorge Pedro López-Alonso

    (Bizkaia Technology Park
    Instituto Biofisika (CSIC - UPV/EHU))

  • Melisa Lázaro

    (Bizkaia Technology Park)

  • David Gil-Cartón

    (Bizkaia Technology Park
    Basque Foundation for Science
    Instituto Biofisika (CSIC - UPV/EHU))

  • Philip H. Choi

    (Columbia University)

  • Alexandra Dodu

    (Bizkaia Technology Park)

  • Liang Tong

    (Columbia University)

  • Mikel Valle

    (Bizkaia Technology Park)

Abstract

Pyruvate carboxylase (PC) is a tetrameric enzyme that contains two active sites per subunit that catalyze two consecutive reactions. A mobile domain with an attached prosthetic biotin links both reactions, an initial biotin carboxylation and the subsequent carboxyl transfer to pyruvate substrate to produce oxaloacetate. Reaction sites are at long distance, and there are several co-factors that play as allosteric regulators. Here, using cryoEM we explore the structure of active PC tetramers focusing on active sites and on the conformational space of the oligomers. The results capture the mobile domain at both active sites and expose catalytic steps of both reactions at high resolution, allowing the identification of substrates and products. The analysis of catalytically active PC tetramers reveals the role of certain motions during enzyme functioning, and the structural changes in the presence of additional cofactors expose the mechanism for allosteric regulation.

Suggested Citation

  • Jorge Pedro López-Alonso & Melisa Lázaro & David Gil-Cartón & Philip H. Choi & Alexandra Dodu & Liang Tong & Mikel Valle, 2022. "CryoEM structural exploration of catalytically active enzyme pyruvate carboxylase," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33987-2
    DOI: 10.1038/s41467-022-33987-2
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    References listed on IDEAS

    as
    1. Christine S. Huang & Kianoush Sadre-Bazzaz & Yang Shen & Binbin Deng & Z. Hong Zhou & Liang Tong, 2010. "Crystal structure of the α6β6 holoenzyme of propionyl-coenzyme A carboxylase," Nature, Nature, vol. 466(7309), pages 1001-1005, August.
    2. Yumeng Liu & Melissa M. Budelier & Katelyn Stine & Martin St. Maurice, 2018. "Allosteric regulation alters carrier domain translocation in pyruvate carboxylase," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    3. Jia Wei & Liang Tong, 2015. "Crystal structure of the 500-kDa yeast acetyl-CoA carboxylase holoenzyme dimer," Nature, Nature, vol. 526(7575), pages 723-727, October.
    4. Ewen Callaway, 2020. "Revolutionary cryo-EM is taking over structural biology," Nature, Nature, vol. 578(7794), pages 201-201, February.
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