Multifunctional protein CAD dihydroorotase domain (Human dihydroorotase refers to the dihydroorotase domain within CAD, not a standalone protein in humans) (DHOase)

The *human dihydroorotase* refers specifically to the dihydroorotase domain of the large, multifunctional CAD protein, which catalyzes the third step in the *de novo* biosynthesis of pyrimidine nucleotides (conversion of N-carbamoyl-L-aspartate to dihydroorotate). This enzymatic activity is crucial for the production of nucleotides required for DNA and RNA synthesis, and its upregulation is essential for cell proliferation, especially in rapidly dividing cancer cells. Unlike bacteria, humans do not have a standalone dihydroorotase protein—this domain is one of three enzymatic centers within CAD, alongside carbamoyl phosphate synthetase and aspartate transcarbamoylase. Structural studies show a highly conserved active site containing a flexible lid loop and Zn^2+ ions, making parts of the CAD dihydroorotase an attractive drug target. Notably, 5-fluorouracil, a widely used anticancer agent, binds the human dihydroorotase domain, expanding its pharmacological relevance. Targeting dihydroorotase with inhibitors disrupts pyrimidine synthesis, restricting cell proliferation—a mechanism central to many anti-cancer drugs.

Other names

Dihydroorotase domain of CADhuDHOaseDHOase (Human)CAD dihydroorotase domain

Inhibition of pyrimidine biosynthesis (by blocking the dihydroorotase domain/CAD enzymatic activity); Direct binding to the active site (dynamic loop, as seen for 5-FU binding)