Zinc Binding Alcohol Dehydrogenase Domain Containing 2 (ZADH2) is a protein that belongs to the zinc-containing alcohol dehydrogenase family. This family of enzymes plays a crucial role in the metabolism of alcohols and aldehydes, converting them into their corresponding aldehydes and ketones, respectively. ZADH2 is encoded by the ZADH2 gene, which is located on human chromosome 18q22.3 .
ZADH2 is a 377 amino acid protein that contains a zinc-binding domain essential for its catalytic activity . The protein is characterized by its ability to bind zinc ions, which are critical for its enzymatic function. Zinc ions play a dual role in the enzyme’s structure and function: one zinc ion is involved in the catalytic activity, while the other contributes to the structural stability of the enzyme .
The enzyme operates as a dimer or tetramer, with each subunit comprising two primary structural domains: a catalytic domain and a coenzyme-binding domain. The catalytic domain is responsible for the enzyme’s activity, while the coenzyme-binding domain binds to NAD (H) or NADP (H) co-factors, which are necessary for the enzyme’s function .
ZADH2 is involved in the conversion of 15-keto-prostaglandin E2 to 13,14-dihydro-15-keto-prostaglandin E2. This reaction is significant in the regulation of prostaglandin levels, which are important mediators in various physiological processes, including inflammation and adipocyte differentiation . The enzyme also plays a role in controlling the activity of peroxisome proliferator-activated receptor gamma (PPARγ), a key regulator of adipogenesis .
The ZADH2 gene is located on chromosome 18, which houses over 300 protein-coding genes. Mutations or defects in genes located on chromosome 18 can lead to various diseases, including Trisomy 18 (Edwards syndrome), Niemann-Pick disease, hereditary hemorrhagic telangiectasia, erythropoietic protoporphyria, and follicular lymphomas .
Human recombinant ZADH2 is typically expressed in Escherichia coli (E. coli) systems. The recombinant protein is purified using affinity chromatography techniques, often involving a His-tag for easy purification . The purified protein is used in various research applications, including blocking assays and control experiments .