Allantoinase (ALLase)

Allantoinase (EC 3.5.2.5) is a key enzyme in the purine degradation pathway that catalyzes the hydrolytic cleavage of the hydantoin ring of (S)-allantoin to produce allantoic acid (Wikipedia; PMC9857997). While absent in humans and other higher primates, it is widely distributed in bacteria, fungi, plants, and lower animals, where it facilitates nitrogen recycling from purine nucleotides (UniProt; Company of Biologists). In many pathogenic bacteria, allantoinase is essential for utilizing purines as a nitrogen source, making it a viable target for the development of novel antimicrobial agents (PubMed 24418229; PMC9857997). The enzyme belongs to the cyclic amidohydrolase family and typically contains a binuclear metal center, often zinc or cobalt, which is crucial for its catalytic mechanism (UniProt; PMC9857997). Although no drugs targeting allantoinase are currently approved for clinical use, experimental studies have identified several natural flavonols, such as kaempferol and myricetin, as potent competitive inhibitors (PubMed 24418229). Because the enzyme is not present in the human genome, inhibitors targeting bacterial allantoinase offer a strategy for selective toxicity with potentially fewer side effects in the host (PMC9857997). In clinical research, its substrate, allantoin, is frequently monitored as a biomarker for oxidative stress and metabolic dysfunction in humans (MDPI; PubMed 34799310).

Other names

(S)-allantoin amidohydrolaseAllantoin-utilizing enzymeAllBALN

Competitive inhibition of the enzyme's binuclear metal active site, preventing the hydrolysis of allantoin to allantoate, which disrupts purine catabolism and nitrogen salvage in pathogens.