Dihydrodipicolinate reductase

The overall fold of MIPS is similar to that of diaminopimelic acid dehydrogenase from Corynebacterium glutamicum and dihydrodipicolinate reductase from E. coli. Though the reactions catalyzed by these enzymes are quite different, they all use either NAD+ or NADP+ bound to a structurally similar Rossmann fold domain, and all three contain a (3 sheet domain located underneath the Rossmann fold and directly beneath the nicotinamide moiety that defines part of the active site (Norman et al., 2002 Stein and Geiger, 2002). 

Fig. 3. CLM (common ligand mimic) with linker to SL (substrate ligand) is prepared by computationally matching the pharmacophore properties of the nicotinamide ring of NADH bound to dihydrodipicolinate reductase (DHPR) (11).

Cirilli, M., Zheng, R., Scapin, G., and Blanchard, J.S. (2003) 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, 10644-10650. 

Aspartate 4-semialdehyde, seen, for example, in Scheme 12.13, which provided a pathway for the biosynthesis of the essential amino acid methionine (Met, M) and in Scheme 12.14, which holds a representation of the biosynthesis of threonine (Thr, T), is also a place to begin to describe a pathway to lysine (Lys, K). As shown in Scheme 12.19, aspartate 4-semialdehyde undergoes an aldol-type reaction with pyruvate (CHsCOCO ") in the presence of dihydropicoUnate synthase (EC 4.2.1.52) to produce a series of intermediates that, it is presumed, lead to (5)-23-dihydropyridine-2,6-dicarboxylate. Then, dihydrodipicolinate reductase (EC 1.3.1.26) working with NADPH produces the tetrahydropyridine, (S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate.This heterocycle, in the presence of glutamate (Glu, E) and water, is capable of transamination directly to 2-oxoglutarate and (2S, 6S)-2,3-diaminopimelate in the presence of LL-diaminopimelate aminotransferase (EC 2.6.1.83), while the latter, in the presence of the pyridoxal dependent racemase... 

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