Publication: Creation of a zymogen
Issued Date
2003-02-01
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ISSN
10728368
DOI
Other identifier(s)
2-s2.0-0037313263
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Mahidol University
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SCOPUS
Bibliographic Citation
Nature Structural Biology. Vol.10, No.2 (2003), 115-119
Suggested Citation
Parit Plainkum, Stephen M. Fuchs, Suthep Wiyakrutta, Ronald T. Raines Creation of a zymogen. Nature Structural Biology. Vol.10, No.2 (2003), 115-119. doi:10.1038/nsb884 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/20764
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Title
Creation of a zymogen
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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.