7ZZ8

Cryo-EM structure of Lactococcus lactis pyruvate carboxylase with acetyl-CoA and cyclic di-AMP

Summary for 7ZZ8

• Entry DOI: 10.2210/pdb7zz8/pdb
• EMDB information: 15037
• Descriptor: Pyruvate carboxylase, MAGNESIUM ION, MANGANESE (II) ION, ... (8 entities in total)
• Functional Keywords: tetramer, carboxylase, biotin, inhibitor, ligase
• Biological source: Lactococcus lactis
• Total number of polymer chains: 4
• Total formula weight: 516428.66

Authors

Lopez-Alonso, J.P.,Lazaro, M.,Gil, D.,Choi, P.H.,Tong, L.,Valle, M. (deposition date: 2022-05-25, release date: 2022-10-12, Last modification date: 2023-11-15)

Primary citation

Lopez-Alonso, J.P.,Lazaro, M.,Gil-Carton, D.,Choi, P.H.,Tong, L.,Valle, M.
CryoEM structural exploration of catalytically active enzyme pyruvate carboxylase.
Nat Commun, 13:6185-6185, 2022

PubMed 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.

PubMed: 36261450
DOI: 10.1038/s41467-022-33987-2

Experimental method

ELECTRON MICROSCOPY (3.29 Å)