Diaminopimelate decarboxylase (DAPDC) catalyses the irreversible stereospecific decarboxylation of meso-diaminopimelate to l-lysine. This is the final step in the diaminopimelate biosynthesis pathway of bacteria, which produces important building blocks for cell wall and protein synthesis. Lysine is an essential amino acid for humans; therefore inhibition of this enzyme should lead to bacterial cell death without incurring toxic effect on humans, as there is no homologous enzyme in humans.

The active site of the enzyme is formed by residues from two interacting monomers, and thus the dimeric structure is hypothesised to be important for the function of the enzyme. There are several X-ray crystallography structures of DAPDC from different species deposited in the PDB. These structures exist either as dimers or tetramers in the crystal state. However, the quaternary structure of the DAPDC enzymes has not been thoroughly characterised in solution. Consequently, the aim of this study is to elucidate the biologically-relevant quaternary structure of DAPDC that is required for activity. Accordingly, it is hypothesised that dimerisation is indispensable to the activity of DAPDC.

In this study, DAPDC from Gram-Negative mesophiles (Escherichia coli and Vibrio cholera); a Gram-Negative psychrophile (Psychromonas ingrahamii); a Gram-Negative thermophile (Thermotoga maritima);an acid-fast bacterium (Mycobacterium tuberculosis); and a Gram-Positive mesophile (Bacillus anthracis) have been subjected to analytical ultracentrifugation (AUC) to clarify the in solution quaternary structure. Additionally, V. cholerae DAPDC has been subjected to SAXS to further probe the in solution quaternary structure, with the results agreeing with AUC and X-ray crystallographic data. Mutational studies on V. cholerae, to engineer monomers, have also been completed to examine the activity of monomeric DAPDC. X-ray crystallography has been engaged on DAPDCs that have as yet not been solved. It has been discovered that the quaternary structure from these different bacterial species agrees well with what is seen in the crystal structures.