ArticleNature structural biology2003
Creation of a zymogen.
Article in Nature structural biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Sensitive detection of SARS-CoV-2 main protease 3CLProtein science : a publication of the Protein Society · 2024Article
- Massively parallel, computationally guided design of a proenzyme.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Ribonuclease zymogen induces cytotoxicity upon HIV-1 infection.AIDS research and therapy · 2021Article
- Circular zymogens of human ribonuclease 1.Protein science : a publication of the Protein Society · 2019Article
- Development of latent Interferon alpha 2b as a safe therapeutic for treatment of Hepatitis C virus infection.Scientific reports · 2019Article
- Development and structural characterization of an engineered multi-copper oxidase reporter of protein-protein interactions.The Journal of biological chemistry · 2019Article
- Article
- Engineering carboxypeptidase G2 circular permutations for the design of an autoinhibited enzyme.Protein engineering, design & selection : PEDS · 2017Article
- Tolerance of a Knotted Near-Infrared Fluorescent Protein to Random Circular Permutation.Biochemistry · 2016Article
- The Structure of a Thermophilic Kinase Shapes Fitness upon Random Circular Permutation.ACS synthetic biology · 2016Article
- Protease-based synthetic sensing and signal amplification.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Article
- Article
- Rational design and evaluation of mammalian ribonuclease cytotoxins.Methods in enzymology · 2012Article
- Ribonuclease S redux.Chemical communications (Cambridge, England) · 2011Article
- Engineered toxins "zymoxins" are activated by the HCV NS3 protease by removal of an inhibitory protein domain.PloS one · 2011Article
- Converting a protein into a switch for biosensing and functional regulation.Protein science : a publication of the Protein Society · 2011Review
- Protease activation of split green fluorescent protein.Chembiochem : a European journal of chemical biology · 2010Article
- Engineering an artificial zymogen by alternate frame protein folding.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Analysis of p300/CBP histone acetyltransferase regulation using circular permutation and semisynthesis.Journal of the American Chemical Society · 2010Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.