PAICS Human

PAICS is a bifunctional enzyme that consists of two domains: the N-terminal domain, which has phosphoribosylaminoimidazole carboxylase activity, and the C-terminal domain, which has phosphoribosylaminoimidazole succinocarboxamide synthetase activity. This bifunctional nature allows PAICS to catalyze two sequential steps in the purine biosynthesis pathway .

In humans, PAICS is encoded by the PAICS gene located on chromosome 4. The enzyme functions as an octamer, with each subunit contributing to the overall activity of the enzyme . The crystal structure of human recombinant PAICS has provided insights into its quaternary structure and the channeling of substrates between its active sites .

The de novo purine biosynthesis pathway is essential for the production of purine nucleotides, which are vital components of DNA, RNA, and various cofactors. PAICS, as a key enzyme in this pathway, is crucial for cellular proliferation and survival. Dysregulation of purine biosynthesis can lead to various diseases, including cancer .

Recent studies have highlighted the importance of PAICS in cancer biology. For instance, PAICS has been identified as a potential therapeutic target for acute myeloid leukemia (AML). Inhibition of PAICS enzymatic activity has been shown to induce cell cycle arrest and apoptosis in AML cells, suggesting that targeting PAICS could be a promising strategy for cancer treatment .

Human recombinant PAICS is produced using recombinant DNA technology, which involves cloning the PAICS gene into an expression vector and introducing it into a suitable host organism, such as Escherichia coli. The host organism then expresses the PAICS protein, which can be purified and used for various research and therapeutic applications.

Recombinant PAICS is valuable for studying the enzyme’s structure, function, and role in disease. It also provides a platform for developing and testing potential inhibitors that could be used as therapeutic agents.