Trifunctional purine biosynthetic protein adenosine-3 (GART)

Trifunctional purine biosynthetic protein adenosine-3 is a human enzyme encoded by the GART gene[1][7]. This multi-domain protein catalyzes three key steps in the de novo purine biosynthesis pathway: - Conversion of 5-phosphoribosylamine (PRA) to glycinamide ribonucleotide (GAR) (by the GARS domain) - Conversion of GAR to N-formylglycinamide ribonucleotide (FGAR) (by the GART/transformylase domain) - Conversion of N-formylglycinamidine ribonucleotide (FGAM) to aminoimidazole ribonucleotide (AIR) (by the AIRS domain)[2][7] This pathway is essential for generating inosine monophosphate (IMP), the precursor for both adenine and guanine nucleotides[1][2][7]. The enzyme plays a crucial role in rapidly proliferating cells, including cancer cells, where de novo purine synthesis is upregulated to meet demand for nucleotides[2][5]. Trifunctional purine biosynthetic protein adenosine-3 is a potential therapeutic target in oncology, as its pathway is essential for nucleotide supply and cell proliferation, especially under conditions of purine deficit or in highly proliferative states[2][5]. However, there are currently no approved drugs that directly target GART for clinical use. Safety concerns for potential therapeutic targeting relate to disruption of nucleotide synthesis in healthy, rapidly dividing cells. Key notes: - The GART protein is essential for cell viability due to its necessity in DNA/RNA synthesis through purine generation[1][2][7]. - Its activity provides a functional metabolic link between amino acid and nucleotide biosynthesis, with importance in both normal physiology and disease, particularly cancer[2][5]. - No existing, approved drugs directly target GART as of now. - Mechanism-based toxicities for potential inhibitors mirror those seen with other antimetabolites, such as myelosuppression (inferred).

Other names

GARTtrifGARTPhosphoribosylglycinamide formyltransferase (domain)Glycinamide ribonucleotide synthetase (domain)Aminoimidazole ribonucleotide synthetase (domain)

Inhibitors would likely act as enzyme inhibitors in the de novo purine biosynthetic pathway.