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Dimerization of Bacterial Diaminopimelate Decarboxylase Is Essential for Catalysis

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posted on 2023-02-02, 22:35 authored by MG Peverelli, Tatiana Soares-da-CostaTatiana Soares-da-Costa, N Kirby, Matthew PeruginiMatthew Perugini
Diaminopimelate decarboxylase (DAPDC) catalyzes the final step in the diaminopimelate biosynthesis pathway of bacteria. The product of the reaction is the essential amino acid L-lysine, which is an important precursor for the synthesis of the peptidoglycan cell wall, housekeeping proteins, and virulence factors of bacteria. Accordingly, the enzymeisapromising antibacterial target. Previous structural studies demonstrate that DAPDC exists as monomers, dimers, and tetramers in the crystal state. However, the active oligomeric form has not yet been determined. We show using analytical ultracentrifugation, small angle x-ray scattering, and enzyme kinetic analyses in solution that the active form of DAPDC from Bacillus anthracis, Escherichia coli, Mycobacterium tuberculosis, and Vibrio cholerae is a dimer. The importance of dimerization was probed further by generating dimerization interface mutants (N381A and R385A) of V. cholerae DAPDC. Our studies indicate that N381A and R385A are significantly attenuated in catalytic activity, thus confirming that dimerization of DAPDC is essential for function. These findings provide scope for the development of new antibacterial agents that prevent DAPDC dimerization.


This work was supported in part by Australian Research Council (ARC) Discovery Project DP150103313. The authors declare that they have no conflicts of interest with the contents of this article.Supported by National Health and Medical Research Council of Australia Grant APP1091976 for fellowship support.


Publication Date



Journal of Biological Chemistry






11p. (p. 9785-9795)


American Society for Biochemistry and Molecular Biology



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© 2016 by The American Society for Biochemistry and Molecular Biology, Inc This is an open access article under the CC BY license:

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