InterPro domain: IPR005263

4-hydroxy-tetrahydrodipicolinate synthase dapA is a homotetrameric enzyme of lysine biosynthesis. It catalyses the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA) [ 1 ]. E. coli has several paralogs closely related to dihydrodipicoline synthase, as well as the more distant N-acetylneuraminate lyase.

It is worth noting that despite the real product of this enzyme being 4-hydroxy-2,3,4,5-tetrahydro-L,L-dipicolinic acid, it is still known in most publications as dihydropicolinate synthase (DHDPS).

The sequences of dapA from different sources are well-conserved. Thestructure takes the form of a homotetramer, in which 2 monomers arerelated by an approximate 2-fold symmetry [ 2 ]. Each monomer comprises 2 domains: an 8-fold alpha-/beta-barrel, and a C-terminal alpha-helical domain. The fold resembles that of N-acetylneuraminate lyase. The active site lysine is located in the barrel domain, and has access via 2 channels on the C-terminal side of the barrel [ 3 ].

1. Enzymology of bacterial lysine biosynthesis. Adv. Enzymol. Relat. Areas Mol. Biol. 72, 279-324
2. The crystal structure of dihydrodipicolinate synthase from Escherichia coli at 2.5 A resolution. J. Mol. Biol. 246, 227-39
3. The crystal structure of three site-directed mutants of Escherichia coli dihydrodipicolinate synthase: further evidence for a catalytic triad. J. Mol. Biol. 338, 329-39