InterPro: IPR011342 Quinate/shikimate 5-dehydrogenase

The shikimate pathway links the metabolism of carbohydrates to the biosynthesis of aromatic compounds and is essential for the biosynthesis of aromatic amino acids and other aromatic compounds in bacteria, eukaryotic microorganisms and plants [1]. It is a seven-step pathway which converts phosphoenolpyruvate and erythrose 4-phosphate to chorismate, the common precursor for the synthesis of folic acid, ubiquinone, vitamins E and K, and aromatic amino acids. Since this pathway is absent in metazoans, which must therefore obtain the essential amino acids phenylalanine and tryptophan from their diet, the enzymes in this pathway are important targets for the development of novel herbicides and antimicrobial compounds.

This entry represents shikimate 5-dehydrogenases from prokaryotes and functionally equivalent C-terminal domains from larger, multifunctional proteins, the majority of which have an N-terminal quinate dehydrogenase domain. These multifunctional proteins occur in plants, chlamydiae, planctomycetes and a limited number of marine proteobacteria. Shikimate 5-dehydrogenase catalyses the fourth step of the shikimate pathway, which is the NADP-dependent reduction of 3-dehydroshikimate to shikimate [2].

Structural studies suggests that some shikimate dehydrogenases are monmers while others form homodimers [3, 4]. Each shikimate dehydrogenase monomer forms a compact two-domain alpha/beta sandwich with a deep interdomain cleft. The N-terminal substrate-binding domain forms a three layer alpha-beta-alpha sandwich, while the C-terminal NADP-binding domain forms a nearly typical Rossman fold. The active site is thought to be located within the interdomain cleft, with substrate binding causing a conformational change which closes the active site cleft, forming a productive active site.