Background: Uracil DNA glycosylases are DNA repair enzymes involved in the removal of base damage. Results: Family 5 UDGb is a uracil, hypoxanthine, and xanthine DNA glycosylase. Conclusion: Family 5 UDGb adapts multiple catalytic amino acids for the excision of pyrimidine and purine deaminated DNA bases. Significance: Family 5 UDGb exemplifies functional diversity in enzyme superfamilies.