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GART is a trifunctional enzyme essential for the de novo purine biosynthesis pathway. It catalyzes three distinct reactions: glycinamide ribonucleotide synthetase (GARS), aminoimidazole ribonucleotide synthetase (AIRS), and glycinamide ribonucleotide formyltransferase (GARTfase). Specifically, the GART domain catalyzes the formation of N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide from glycinamide ribonucleotide using 10-formyltetrahydrofolate as a cofactor. The folate-binding region is targeted by antifolate chemotherapeutic agents, disrupting nucleotide synthesis required for cell proliferation.
Inhibition of folate-binding site, disrupting nucleotide synthesis
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