InterPro domain: IPR023940

Dihydrodipicolinate reductase (DHDPR), a product of an essential gene referred to as dapB, catalyzes the second step of lysine biosynthesis [ 1 , 2 ]. It catalyses the reduction of 2,3-dihydrodipicolinate (DHDP) to 2,3,4,5-tetrahydrodipicolinate (THDP) in a nucleotide dependent reaction [ 3 ]:

2,3-dihydrodipicolinate + NAD(P)H = 2,3,4,5-tetrahydrodipicolinate + NAD(P)(+)

Interestingly, DHDPR could also function as a dehydratase in addition to the role of a nucleotide dependent reductase [ 4 ].

The structures of the Escherichia coli ( P04036 ) and Mycobacterium tuberculosis ( P72024 ) enzymes have been determined [ 5 , 6 ]. The enzyme is a homotetramer where each monomer is composed of two domains, an N-terminal NAD(P)H-binding domain which forms a Rossman fold, and a C-terminal substrate-binding domain that forms an open, mixed alpha-beta sandwich.Tetramerisation occurs exclusively through interactions between C-terminal domain residues. Both enzymes show relatively little preference for either NADH or NADPH as cofactor. Conformational changes upon substrate binding bring the cofactor and substrate into close proximity and allow catalysis to occur.

As this enzyme is not found in mammals it is a potential target for the development of novel antibacterial and herbicidal compounds.

1. Structure and nucleotide specificity of Staphylococcus aureus dihydrodipicolinate reductase (DapB). FEBS Lett. 585, 2561-7
2. Cloning, expression, crystallization and preliminary structural studies of dihydrodipicolinate reductase from Acinetobacter baumannii. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 69, 653-6
3. Reaction mechanism of Escherichia coli dihydrodipicolinate synthase investigated by X-ray crystallography and NMR spectroscopy. Biochemistry 36, 24-33
4. NMR studies uncover alternate substrates for dihydrodipicolinate synthase and suggest that dihydrodipicolinate reductase is also a dehydratase. J. Med. Chem. 53, 4808-12
5. Three-dimensional structure of Escherichia coli dihydrodipicolinate reductase. Biochemistry 34, 3502-12
6. The three-dimensional structures of the Mycobacterium tuberculosis dihydrodipicolinate reductase-NADH-2,6-PDC and -NADPH-2,6-PDC complexes. Structural and mutagenic analysis of relaxed nucleotide specificity. Biochemistry 42, 10644-50