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Title: Creation of a zymogen
Authors: Parit Plainkum
Stephen M. Fuchs
Suthep Wiyakrutta
Ronald T. Raines
University of Wisconsin Madison
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Feb-2003
Citation: Nature Structural Biology. Vol.10, No.2 (2003), 115-119
Abstract: 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.
ISSN: 10728368
Appears in Collections:Scopus 2001-2005

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