Toward the smallest active subdomain of a TIM-barrel fold: Insights from a truncated α-amylase

► AmyTM is a truncated amylase derived via a reading frame shift. ► It was devoided of the three catalytic residues, but it still retains catalytic activity. ► It reveals the restoration of a primitive active site, which was lost in the course of evolution toward more stable domains. ► It provides new avenues to reveal insights into structure-function relationships of barrel domains.