PurH

PurH is a bifunctional enzyme in the de novo purine biosynthesis pathway, found in many bacteria and archaea. It catalyzes the last two steps of the pathway, converting AICAR into IMP, the immediate precursor to the purine nucleotides AMP and GMP. Its activity is essential for the production of purine nucleotides used in RNA and DNA synthesis.

PurH contains two catalytic domains. The N-terminal AICAR transformylase transfers a formyl group from 10-formyltetrahydrofolate to AICAR, forming FAICAR. The C-terminal IMP cyclohydrolase then hydrolyzes FAICAR to produce IMP, completing the construction of the purine ribonucleotide ring. The overall transformation uses one-carbon donors from tetrahydrofolate to convert AICAR into IMP, enabling subsequent nucleotide synthesis.

In bacteria and archaea, purH is typically encoded by the purH gene and expressed as a single multifunctional polypeptide of roughly five hundred amino acids, localized to the cytosol. In eukaryotes, the functional equivalent is often ATIC (AICAR transformylase/IMP cyclohydrolase), encoded by the ATIC gene in humans and other vertebrates, reflecting a conserved bifunctional design across domains of life.

PurH is considered essential for de novo purine biosynthesis. Loss of function leads to purine auxotrophy and impaired cell growth. Because of its central role and distinct active sites, PurH/ATIC has been investigated as a potential target for antimicrobial and anticancer strategies, with inhibitors developed to modulate purine nucleotide biosynthesis.