Over time and under stressing conditions, proteins are susceptible to a variety of spontaneous covalent modifications. One of the more commonly occurring types of protein damage is deamidation; the conversion of asparagines into aspartyls and isoaspartyls. The physiological significance of isoaspartyl formation is emphasized by the presence of the conserved enzyme, L-isoaspartyl O-methyltransferase (PIMT), whose physiological function appears to be in preventing the accumulation of deamidated proteins. Seemingly consistent with a repair function, over-expression of PIMT in Drospholia melanogaster extends lifespan under conditions expected to contribute to protein damage. Based on structural information and sequence homology we have created mutants of residues proposed to be involved in co-factor binding in Escherichia coli PIMT. Both mutants retain S-adenosyl L-methionine binding capabilities but demonstrate dramatically reduced kinetic capabilities, perhaps suggestive of catalytic roles beyond co-factor binding. As anticipated, over-expression of the wild type enzyme in Escherichia coli results in bacteria with increased tolerance to thermal stress. Surprisingly even greater levels of heat tolerance were observed with over-expression of the inactive PIMT mutants. The increased survival capabilities observed with over expression of PIMT in E. coli, and likely in Drospholia, are not due to increased isoaspartyl repair capabilities but rather a temperature-independent induction of the heat-shock system as a result of over-expression of a misfolding prone protein. An alternate hypothesis as to the physiological substrate and function of L-isoaspartyl methyltransferase is proposed.