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Creation of a zymogen.


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 approximately 10(3)-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.

SUBMITTER: Plainkum P 

PROVIDER: S-EPMC2819095 | biostudies-literature | 2003 Feb

REPOSITORIES: biostudies-literature

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Creation of a zymogen.

Plainkum Parit P   Fuchs Stephen M SM   Wiyakrutta Suthep S   Raines Ronald T RT  

Nature structural biology 20030201 2


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 approximately 10(3)-fold in catalytic activity and maintains high conformati  ...[more]

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