The C-terminal domain of Escherichia coli dihydrodipicolinate synthase (DHDPS) is essential for maintenance of quaternary structure and efficient catalysis.

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.