Shikimate dehydrogenase

This pathway is found in bacteria, plants, fungi, algae, and parasites and is responsible for the biosynthesis of aromatic amino acids (phenylalanine, tyrosine, and tryptophan) from the metabolism of carbohydrates.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor.

[1] The domains of the monomer show a fair amount of flexibility suggesting that the enzyme can open in close to bind with the substrate 3-Dehydroshikimate.

The two forms of shikimate dehydrogenase have different primary sequences in different organisms but catalyze the same reactions.

[3] They both have high affinity of their ligands as shown by their similar enzyme (Km) values.

In order to design new inhibitors the structures for all the enzymes in the pathway have needed to be elucidated.

The presence of two forms of the enzyme complicate the design of potential drugs because one could compensate for the inhibition of the other.

Also there the TIGR data base shows that there are 14 species of bacteria with the two forms of shikimate dehydrogenase.

The Shikimate Dehydrogenase Reaction
The cleft in the shikimate dehydrogenase monomer. The green selection is the loops surrounding the cleft, and the red selection shows alpha helices in the background.
Shikimate dehydrogenase YdiB with highlighted NADH binding sites. The red color of the surface of the structure shows alpha helices, the yellow shows beta sheets, and the green area shows where there are loops in the enzyme.
The AroE form of shikimate dehydrogenase with highlighted NADP + binding sites. The red color shows where the alpha helices are, the green shows the loops, and the yellow shows the beta sheets in the structure.