Dihydrodipicolinate synthase (DHDPS) catalyses the first committed step in the biosynthesis of (S)-lysine, an essential constituent of bacterial cell walls. Escherichia coli DHDPS is homotetrameric, and each monomer contains an N-terminal (alpha/beta)(8)-barrel, responsible for catalysis and regulation, and three C-terminal alpha-helices, the function of which is unknown. This study investigated the C-terminal domain of E. coli DHDPS by characterising a C-terminal truncated DHDPS (DHDPS-H225*). DHDPS-H225* was unable to complement an (S)-lysine auxotroph, and showed significantly reduced solubility, stability, and maximum catalytic activity (k(cat)=1.20+/-0.01 s(-1)), which was only 1.6% of wild type E. coli DHDPS (DHDPS-WT). The affinity of DHDPS-H225* for substrates and the feedback inhibitor, (S)-lysine, remained comparable to DHDPS-WT. These changes were accompanied by disruption in the quaternary structure, which has previously been shown to be essential for efficient catalysis in this enzyme.