2-dehydro-3-deoxy-D-gluconate aldolase (KDGA)

2-dehydro-3-deoxy-D-gluconate aldolase, frequently referred to as 2-keto-3-deoxygluconate (KDG) aldolase, is a Class I aldolase enzyme predominantly found in bacteria and archaea. It is a key component of the non-phosphorylative Entner-Doudoroff (ED) pathway, where it catalyzes the reversible retro-aldol cleavage of 2-keto-3-deoxygluconate into pyruvate and D-glyceraldehyde. While this pathway is absent in humans, it is essential for the metabolism of various sugars in several human pathogens, making the enzyme a potential target for the development of narrow-spectrum antimicrobial agents. The enzyme is also highly valued in biocatalysis for its ability to facilitate the stereoselective synthesis of complex carbohydrates and chiral intermediates used in the pharmaceutical industry. In humans, a closely related homolog known as 4-hydroxy-2-oxoglutarate aldolase (HOGA1) is involved in the degradation of hydroxyproline; mutations in the HOGA1 gene are the primary cause of Primary Hyperoxaluria Type 3, a condition characterized by excessive oxalate production and kidney stone formation. Experimental inhibitors of KDG aldolase typically include pyruvate analogs and other substrate mimetics that form a covalent Schiff base intermediate with a conserved active-site lysine residue.

Other names

2-keto-3-deoxygluconate aldolaseKDG aldolase2-oxo-3-deoxygluconate aldolase2-dehydro-3-deoxy-6-phosphogluconate aldolase (ambiguous)KDPG aldolase (ambiguous)

Covalent Schiff base formation with a conserved active-site lysine residue (Class I aldolase mechanism) to facilitate the reversible cleavage of 2-keto-3-deoxygluconate into pyruvate and D-glyceraldehyde.