Diaminopimelate decarboxylase

DAPDC is a PLP-dependent enzyme belonging to the alanine racemase family. This enzyme is generally dimeric with each monomer containing two domains. The first domain is the N-terminal α/β-barrel that binds the PLP to the active site lysine residue. The tetramer is shaped like a ring with the active sites accessible from the inside of the enzyme. == Mechanism ==

The first step in the mechanism is the formation of a Schiff base with the substrate amino group. DAPDC then uses the interaction of 3 residues (Arginine, Aspartate, and Glutamate) within the active site to identify the D-stereocenter. The DAP is decarboxylated and then stabilized by PLP. It is not clear which general acid protonates after decarboxylation, but there is speculation that the lysine residue is the donor. == Regulation ==

DAPDC is regulated by the product L-lysine at relatively high concentrations. Compounds that are similar to DAP in chemical complexity do not inhibit the reaction, possibly due to the residue rulers creating specific bond angles. Diamines have a stronger inhibitory effect compared to dicarboxylic acids, most likely from interactions with PLP. == Function ==

Given that there are three pathways to convert aspartate to lysine, this is clearly an essential process for the cell, particularly in building cell walls in Gram-positive bacteria. There is no process for producing lysine in humans, but ornithine decarboxylase shares many similarities with DAPDC. Both enzymes use PLP as a cofactor and have similar structures forming the active sites. However, DAPDC differs in that it decarboxylates at the D-stereocenter and is highly stereospecific. These unique features make DAPDC a good candidate for antibacterial studies because potential inhibitors of such an integral step in cell viability would be unlikely to interact with necessary processes within humans. == References ==