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Creation of a zymogen

2002; Nature Portfolio; Volume: 10; Issue: 2 Linguagem: Inglês

10.1038/nsb884

1545-9993

Parit Plainkum, Stephen M. Fuchs, Suthep Wiyakrutta, Ronald T. Raines,

Biochemical and Structural Characterization

Cells 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.