We have evaluated the roles of key amino acids to the action of the natural inhibitor chagasin of papain-family cysteine peptidases. A W93A substitution decreased inhibitor affinity for human cathepsin L 100-fold, while substitutions of T31 resulted in 10-100-fold increases in the Ki for cruzipain of Trypanosoma cruzi. A T31A/T32A double mutant had increased affinity for cathepsin L but not for cruzipain, while the T31-T32 deletion drastically affected inhibition of both human and parasite peptidases. These differential effects reflect the occurrence of direct interactions between chagasin and helix 8 of cathepsin L, interactions that do not occur with cruzipain.
- cysteine peptidase
Dos Reis, F. C. G., Smith, B. O., Santos, C. C., Costa, T. F. R., Scharfstein, J., Coombs, G. H., Mottram, J. C., & Lima, A. P. C. A. (2008). The role of conserved residues of chagasin in the inhibition of cysteine peptidases. FEBS Letters, 582(4), 485-490. https://doi.org/10.1016/j.febslet.2008.01.008