Parit PlainkumStephen M. FuchsSuthep WiyakruttaRonald T. RainesUniversity of Wisconsin MadisonMahidol University2018-07-242018-07-242003-02-01Nature Structural Biology. Vol.10, No.2 (2003), 115-119107283682-s2.0-0037313263https://repository.li.mahidol.ac.th/handle/20.500.14594/20764Cells produce proteases as inactive zymogens. Here, we demonstrate that this tactic can extend beyond proteases. By linking the N and C termini of ribonuclease A, we obstruct the active site with the amino acid sequence recognized by plasmepsin II, a highly specific protease from Plasmodium falciparum. We generate new N and C termini by circular permutation. In the presence of plasmepsin II, a ribonuclease zymogen gains ∼103-fold in catalytic activity and maintains high conformational stability. We conclude that zymogen creation provides a new and versatile strategy for the control of enzymatic activity, as well as the potential development of chemotherapeutic agents.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1038/nsb884