ArticleBiochemistry2011
Post-translational phosphorylation of serine 74 of human deoxycytidine kinase favors the enzyme adopting the open conformation making it competent for nucleoside binding and release.
Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- Structure-guided engineering of human thymidine kinase 2 as a positron emission tomography reporter gene for enhanced phosphorylation of non-natural thymidine analog reporter probe.The Journal of biological chemistry · 2012Trial
- Cellular pharmacology of fludarabine: molecular determinants of transport and metabolism.Frontiers in pharmacology · 2026Review
- Optimization and Evaluation of Complementary Degrader Discovery Assays for Application in Screening.ACS pharmacology & translational science · 2025Article
- From a drug repositioning to a structure-based drug design approach to tackle acute lymphoblastic leukemia.Nature communications · 2023Article
- Hypertension: Constraining the Expression of ACE-II by Adopting Optimal Macronutrients Diet Predicted via Support Vector Machine.Nutrients · 2022Article
- Solution structure and functional investigation of human guanylate kinase reveals allosteric networking and a crucial role for the enzyme in cancer.The Journal of biological chemistry · 2019Article
- Article
- Dual protein kinase and nucleoside kinase modulators for rationally designed polypharmacology.Nature communications · 2017Article
- ATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways.Nature communications · 2017Article
- The Role of Deoxycytidine Kinase (dCK) in Radiation-Induced Cell Death.International journal of molecular sciences · 2016Article
- Potent Sensitisation of Cancer Cells to Anticancer Drugs by a Quadruple Mutant of the Human Deoxycytidine Kinase.PloS one · 2015Article
- A phosphotyrosine switch for cargo sequestration at clathrin-coated buds.The Journal of biological chemistry · 2014Article
- Deoxycytidine kinase augments ATM-Mediated DNA repair and contributes to radiation resistance.PloS one · 2014Article
- Structural characterization of new deoxycytidine kinase inhibitors rationalizes the affinity-determining moieties of the molecules.Acta crystallographica. Section D, Biological crystallography · 2014Article
- New insights into the synergism of nucleoside analogs with radiotherapy.Radiation oncology (London, England) · 2013Review
- Mechanistic studies on the synergistic cytotoxicity of the nucleoside analogs gemcitabine and clofarabine in multiple myeloma: relevance of p53 and its clinical implications.Experimental hematology · 2013Article
- Retrovolution: HIV-driven evolution of cellular genes and improvement of anticancer drug activation.PLoS genetics · 2012Article
- Cell fate control gene therapy based on engineered variants of human deoxycytidine kinase.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Deoxycytidine kinase (dCK) uses either ATP or UTP as a phosphoryl donor to catalyze the phosphorylation of nucleoside acceptors. The kinetic properties of human dCK are modulated in vivo by phosphorylation of serine 74. This residue is a part of the insert region and is distant from the active site. Replacing the serine with a glutamic acid (S74E variant) can mimic phosphorylation of Ser74. To understand how phosphorylation affects the catalytic properties of dCK, we examined the S74E variant of dCK both structurally and kinetically. We observe that the presence of a glutamic acid at position 74 favors the adoption by the enzyme of the open conformation. Glu74 stabilizes the open conformation by directly interacting with the indole side chain of Trp58, a residue that is in the proximity of the base of the nucleoside substrate. The open dCK conformation is competent for the binding of nucleoside but not for phosphoryl transfer. In contrast, the closed conformation is competent for phosphoryl transfer but not for product release. Thus, dCK must make the transition between the open and closed states during the catalytic cycle. We propose a reaction scheme for dCK that incorporates the transition between the open and closed states, and this serves to rationalize the observed kinetic differences between wild-type dCK and the S74E variant.
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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.