ArticleJournal of molecular biology2008
Yeast cytosine deaminase mutants with increased thermostability impart sensitivity to 5-fluorocytosine.
Article in Journal of molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 42 citations in OpenAlex.
- DAZL-targeted inducible kill switches enable efficient ablation of chicken primordial germ cells.Poultry science · 2026Article
- An engineered yeast cytosine deaminase with improved catalytic activity and stability for macrophage-mediated enzyme/prodrug therapy.Communications biology · 2025Article
- Engineering the Active Site Lid Dynamics to Improve the Catalytic Efficiency of Yeast Cytosine Deaminase.International journal of molecular sciences · 2023Article
- Review
- A Comprehensive Insight into Fungal Enzymes: Structure, Classification, and Their Role in Mankind's Challenges.Journal of fungi (Basel, Switzerland) · 2021Review
- Prodrugs and prodrug-activated systems in gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Bi-Functional Radiotheranostics ofInternational journal of molecular sciences · 2021Article
- Quantitative evaluation and comparison of two prodrug-activating suicide gene therapies on oral squamous cell carcinoma.American journal of cancer research · 2021Article
- Enzyme Stabilization by Virus-Like Particles.Biochemistry · 2020Article
- Nucleobase deaminases: a potential enzyme system for new therapies.RSC advances · 2018Review
- Progress and problems with the use of suicide genes for targeted cancer therapy.Advanced drug delivery reviews · 2016Review
- Retroviral Replicating Vectors Deliver Cytosine Deaminase Leading to Targeted 5-Fluorouracil-Mediated Cytotoxicity in Multiple Human Cancer Types.Human gene therapy methods · 2016Article
- Adenoviral-mediated imaging of gene transfer using a somatostatin receptor-cytosine deaminase fusion protein.Cancer gene therapy · 2015Article
- Development of inhibitor-directed enzyme prodrug therapy (IDEPT) for prostate cancer.Bioconjugate chemistry · 2014Article
- Advancements in the development of HIF-1α-activated protein switches for use in enzyme prodrug therapy.PloS one · 2014Article
- Enzymes to die for: exploiting nucleotide metabolizing enzymes for cancer gene therapy.Current gene therapy · 2012Review
- Evaluation of a UCMK/dCK fusion enzyme for gemcitabine-mediated cytotoxicity.Biochemical and biophysical research communications · 2011Article
- Comparative analysis of enzyme and pathway engineering strategies for 5FC-mediated suicide gene therapy applications.Cancer gene therapy · 2011Article
- Antitumor activity of mutant bacterial cytosine deaminase gene for colon cancer.World journal of gastroenterology · 2011Article
- Bacterial cytosine deaminase mutants created by molecular engineering show improved 5-fluorocytosine-mediated cell killing in vitro and in vivo.Cancer research · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Prodrug gene therapy (PGT) is a treatment strategy in which tumor cells are transfected with a 'suicide' gene that encodes a metabolic enzyme capable of converting a nontoxic prodrug into a potent cytotoxin. One of the most promising PGT enzymes is cytosine deaminase (CD), a microbial salvage enzyme that converts cytosine to uracil. CD also converts 5-fluorocytosine (5FC) to 5-fluorouracil, an inhibitor of DNA synthesis and RNA function. Over 150 studies of CD-mediated PGT applications have been reported since 2000, all using wild-type enzymes. However, various forms of CD are limited by inefficient turnover of 5FC and/or limited thermostability. In a previous study, we stabilized and extended the half-life of yeast CD (yCD) by repacking of its hydrophobic core at several positions distant from the active site. Here we report that random mutagenesis of residues selected based on alignment with similar enzymes, followed by selection for enhanced sensitization to 5FC, also produces an enzyme variant (yCD-D92E) with elevated T(m) values and increased activity half-life. The new mutation is located at the enzyme's dimer interface, indicating that independent mutational pathways can lead to an increase in stability, as well as a more subtle effect on enzyme kinetics. Each independently derived set of mutations significantly improves the enzyme's performance in PGT assays both in cell culture and in animal models.
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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.