Deaminases

Deaminases are enzymes that catalyze the removal of amino groups from substrates, often resulting in the conversion of one nucleotide to another in nucleic acids or the breakdown of purine and pyrimidine metabolites. In cells, deaminations can alter base pairing, gene expression, and metabolic flux, and they play important roles in immunity, RNA editing, and nucleotide turnover.

In humans, major families include cytidine deaminases, adenosine deaminases, and adenosine deaminases acting on RNA. Cytidine deaminases, such as activation-induced cytidine deaminase (AID) and the APOBEC family, typically deaminate cytidine to uridine in DNA or RNA. Adenosine deaminases remove amino groups from adenosine to produce inosine, with ADARs (adenosine deaminases acting on RNA) editing adenosine to inosine in double-stranded RNA. Other deaminases act on free nucleobases in metabolism, such as guanine deaminase, and bacterial cytosine deaminases.

Biological roles are diverse. AID initiates somatic hypermutation and class switch recombination in immunoglobulin genes, enabling antibody diversity. APOBEC enzymes contribute to antiviral defense by mutating viral genomes and can cause cancer-associated mutational signatures when deregulated. ADA (adenosine deaminase) is essential for purine metabolism; ADA deficiency causes severe combined immunodeficiency. RNA editing by ADARs can alter codons, splicing, and immune sensing. Deaminases also underpin genome-editing technologies, where cytidine deaminases and engineered adenine deaminases form the basis of base editors used in research and potential therapies.

Clinical and research interest focuses on understanding deaminase specificity, regulation, and the consequences of misediting, as well as leveraging these enzymes for therapeutic genome editing.