Bifunctional purine biosynthesis protein ATIC (ATIC)

Bifunctional purine biosynthesis protein ATIC is a cytoplasmic enzyme responsible for catalyzing the final two steps of de novo purine nucleotide biosynthesis. It possesses both phosphoribosylaminoimidazolecarboxamide formyltransferase activity at its N-terminal domain and IMP cyclohydrolase activity at its C-terminal domain. These activities are essential for converting AICAR into FAICAR and then into inosine monophosphate (IMP), a precursor for AMP and GMP nucleotides. The gene encoding this protein is located on chromosome 2q35. Dysregulation or mutation of ATIC impacts cellular proliferation pathways—including those relevant to tumorigenesis—and inherited deficiencies cause rare metabolic diseases like AICA-ribosiduria. Its role makes it an important target for anticancer therapies utilizing antifolates or antimetabolites that disrupt nucleotide production necessary for rapid cell division.

Other names

AICAR transformylase/inosine monophosphate cyclohydrolasePURH5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase

Drugs targeting this molecule typically act as antifolates or antimetabolites that inhibit its enzymatic activities—either blocking the formyltransferase step or the IMP cyclohydrolase step—thereby suppressing nucleotide synthesis required for cell proliferation. This leads to inhibition of DNA/RNA synthesis in rapidly dividing cells such as cancer cells.