Catalytic antibody 16G3, a peptide ligase with extended substrate scope has been characterized mechanistically exploiting a set of systematically designed perspective substrates 6-9, two of which, thioesters 8 and 9 act instead as inhibitors. Taken together the structure/activity relationships suggest a catalytic mechanism dependent on induction of strain, programmed via specific structural deviations between the hapten and the substrates. General mechanistic implications for de novo induced catalysis are presented.