Microbial transglutaminase has a lower deamidation preference than human tissue transglutaminase on a celiac disease relevant wheat gliadin T-cell epitope

Abstract

Tissue transglutaminase (TG2) catalyzed glutamine deamidation within gluten peptides plays a major role in the pathogenesis of celiac disease. Recent studies reported gliadin deamidation by microbial transglutaminase (MTG) and hypothesize an impact on celiac disease incidence. We therefore investigated deamidation and transamidation activities of MTG and human TG2 based on a wheat gliadin peptide containing an immunodominant epitope for celiac disease. Deamidation activity of MTG was about a magnitude lower than transamidation with a maximum at pH 5 and decreasing values at neutral and basic pH. In contrast, TG2-deamidation reaction rate doubled from pH 6 to pH 7. Transamidation activity of MTG showed minor pH dependence, whereas for TG2 it strongly increased from pH 6 to 7 by a factor of 7.5. Additionally, deamidation by TG2 in the presence of a fivefold excess of amine substrate was observed for reactions at pH 6 at an equal rate to transamidation, while at neutral pH no deamidation occurred. MTG only catalyzed deamidation in addition to transamidation when the substrate ratio was below a 2.5 fold excess of amine. In conclusion, transamidation activity rates of MTG and TG2 were higher compared to deamidation rates. In contrast to TG2, MTG shows a strong and pH-independent transamidation preference.