ArticleJournal of molecular biology2007
Non-homologous recombination of deoxyribonucleoside kinases from human and Drosophila melanogaster yields human-like enzymes with novel activities.
Article in Journal of molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- A primer to directed evolution: current methodologies and future directions.RSC chemical biology · 2023Review
- Biological phosphorylation of an Unnatural Base Pair (UBP) using a Drosophila melanogaster deoxynucleoside kinase (DmdNK) mutant.PloS one · 2017Article
- The phylogenetic distribution and evolution of enzymes within the thymidine kinase 2-like gene family in metazoa.Journal of molecular evolution · 2014Article
- Enzymes to die for: exploiting nucleotide metabolizing enzymes for cancer gene therapy.Current gene therapy · 2012Review
- Engineering Kinases to Phosphorylate Nucleoside Analogs for Antiviral and Cancer Therapy.Chimia · 2009Article
- Development of gene therapy in association with clinically used cytotoxic deoxynucleoside analogues.Cancer gene therapy · 2009Review
- Directed evolution of an orthogonal nucleoside analog kinase via fluorescence-activated cell sorting.Nucleic acids research · 2009Article
- Nonpolar nucleoside mimics as active substrates for human thymidine kinases.Journal of the American Chemical Society · 2009Article
- Structure, physiological role, and specific inhibitors of human thymidine kinase 2 (TK2): present and future.Medicinal research reviews · 2008Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In antiviral and cancer therapy, deoxyribonucleoside kinases (dNKs) are often the rate-limiting step in activating nucleoside analog (NA) prodrugs into their cytotoxic, phosphorylated forms. We have constructed libraries of hybrid enzymes by non-homologous recombination of the pyrimidine-specific human thymidine kinase 2 and the broad-specificity dNK from Drosophila melanogaster; their low sequence identity has precluded engineering by conventional, homology-dependent shuffling techniques. From these libraries, we identified chimeras that phosphorylate nucleoside analogs with higher activity than either parental enzyme, and that possess new activity towards the anti-HIV prodrug 2',3'-didehydro-3'-deoxythymidine (d4T). These results demonstrate the potential of non-homologous recombination within the dNK family for creating enzymes with new and improved activities towards nucleoside analogs. In addition, our results exposed a previously unknown role for the C-terminal regions of these dNKs in determining substrate selectivity.
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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.