3-dehydroquinate dehydratase (type II) (DHQ2)

3-Dehydroquinate dehydratase (type II) is an essential enzyme catalyzing the third step in the shikimate pathway: the reversible dehydration of 3-dehydroquinate to 3-dehydroshikimate. This pathway is critical for the biosynthesis of aromatic amino acids and secondary metabolites in bacteria, fungi, and plants, but it does not occur in mammals, making the enzyme an attractive target for antimicrobial and herbicidal compounds. Type II DHQase is structurally characterized as a dodecameric protein (consisting of twelve subunits) with a flavodoxin-like fold. Its reaction mechanism involves proton abstraction by a conserved tyrosine residue and proceeds via an enolate intermediate, in contrast to the Schiff-base mechanism of the type I enzyme. Potent small-molecule inhibitors have been developed by mimicking transition states and by targeting active site residues crucial for catalysis. Because of its absence in animals, the Type II dehydroquinate dehydratase provides a highly selective target for antimicrobial drug discovery.

Other names

Type II dehydroquinaseDehydroquinate dehydratase (type II)3-dehydroquinate dehydratase (type II)DHQ2DHQD (type II)EC 4.2.1.10 (enzyme commission number)

Competitive inhibition of the active site, mimicking the substrate or transition state to block enzyme function and inhibit microorganism growth Some drugs disrupt key active site residues (e.g., by displacing essential arginine, pi-stacking with catalytic tyrosine)