Affinage

DUT

Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial · UniProt P33316

Length
252 aa
Mass
26.6 kDa
Annotated
2026-04-28
100 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DUT (dUTPase) is an essential homotrimeric pyrophosphatase that hydrolyzes dUTP to dUMP and pyrophosphate, thereby maintaining low dUTP/dTTP ratios and preventing uracil misincorporation into DNA. The enzyme assembles via C-terminal β-strand swapping across subunit interfaces, where each active site is formed at the junction of two monomers; substrate binding triggers C-terminal arm closure that positions a nucleophilic water molecule for rate-limiting α-phosphate hydrolysis, accelerated by Mg²⁺ coordination and a conserved aromatic stacking interaction with the uracil base (PMID:1311056, PMID:17880943, PMID:17848562, PMID:20601405, PMID:19302784). Loss of dUTPase activity causes genomic uracil accumulation, iterative base-excision repair, DNA double-strand breaks requiring RecA/RecBCD-dependent recombinational repair, replication stress at fragile sites, and sensitization to thymidylate synthase inhibitors (PMID:14982624, PMID:15322254, PMID:27452458). The nuclear isoform (DUT-N) is targeted to the nucleus by a monopartite NLS (K14R15R17), and its import is negatively regulated by M-phase phosphorylation of Ser11, which weakens importin-α binding (PMID:12799180, PMID:24311590). Homozygous missense mutations in DUT (Y142C/Y54C) cause a monogenic syndrome of early-onset diabetes and bone marrow failure through β-cell apoptosis via the intrinsic cell death pathway (PMID:28073829).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1992 High

    Determination of the first dUTPase crystal structure revealed an unexpected homotrimeric jelly-roll architecture with conserved residues clustered at subunit interfaces, establishing that the active sites are composite structures formed between adjacent monomers.

    Evidence X-ray crystallography of E. coli dUTPase at 1.9 Å resolution

    PMID:1311056

    Open questions at the time
    • No substrate-bound complex to define specificity determinants
    • Human enzyme structure not yet determined
  2. 1996 High

    Co-crystal with a substrate analogue and detailed kinetic characterization defined how the enzyme recognizes dUTP — uracil ring and deoxyribose contacts explain specificity — and established that Mg²⁺ enhances substrate binding ~100-fold and that the rate-limiting step is the chemical hydrolysis of the α-phosphate.

    Evidence X-ray crystallography of E. coli dUTPase–dUDP complex; steady-state and pre-steady-state kinetics with chiral substrates

    PMID:8646539 PMID:8798636

    Open questions at the time
    • Human enzyme mechanism inferred by homology, not directly measured
    • Transition-state structure unresolved
  3. 2003 Medium

    Identification of the monopartite NLS (K14R15R17) in the nuclear isoform DUT-N explained how the two human dUTPase isoforms achieve differential subcellular targeting, resolving a long-standing question about isoform-specific localization.

    Evidence GFP fusion constructs with site-directed mutagenesis and fluorescence microscopy in mammalian cells

    PMID:12799180

    Open questions at the time
    • Phosphorylation of Ser11 did not affect localization in this assay, contradicting later findings — context-dependent regulation not resolved
    • Importin-α binding not directly measured
  4. 2004 High

    Genetic and biochemical studies established that loss of dUTPase triggers a uracil → nick → double-strand break → recombinational repair pathway, and that dUTPase levels directly determine sensitivity to thymidylate synthase inhibitors via dUTP pool expansion and DNA damage.

    Evidence Synthetic lethality screens and PFGE in E. coli dut mutants; siRNA knockdown with nucleotide pool analysis, clonogenic survival, and DSB assays in human cancer cell lines

    PMID:14982624 PMID:15322254

    Open questions at the time
    • Relative contribution of BER versus mismatch repair in mammalian cells not separated
    • Whether dUTPase loss causes replication fork stalling independently of BER not tested
  5. 2007 High

    Crystal structure of human dUTPase with a non-hydrolyzable substrate analogue, combined with pre-steady-state kinetics, defined a complete four-step catalytic cycle and showed that C-terminal arm closure positions the nucleophilic water below van der Waals distance from the α-phosphorus, directly coupling conformational change to catalysis.

    Evidence X-ray crystallography of human dUTPase–α,β-imino-dUTP–Mg²⁺ complex; stopped-flow and quenched-flow kinetics with engineered tryptophan sensor

    PMID:17848562 PMID:17880943

    Open questions at the time
    • Transition-state geometry not fully resolved at atomic level
    • Role of individual active-site residues in human enzyme not dissected by mutagenesis
  6. 2009 High

    Demonstration that C-terminal β-strand swapping is the principal cohesive force for trimer assembly resolved how the obligate trimer architecture is maintained and connected quaternary structure to active-site formation.

    Evidence Crystal structure of a Drosophila dUTPase C-terminal truncation (dimer), SAXS, and mutagenesis of human dUTPase

    PMID:19302784

    Open questions at the time
    • Whether monomer or dimer intermediates exist transiently in vivo not determined
    • Folding pathway from monomer to trimer not characterized
  7. 2010 High

    A conserved aromatic stacking interaction with the uracil base was shown to accelerate catalysis by stabilizing the associative transition state of α-phosphate hydrolysis, revealing a long-range mechanism linking substrate recognition to catalysis.

    Evidence X-ray crystallography, kinetic analysis, optical spectroscopy, and ITC of wild-type and mutant dUTPases

    PMID:20601405

    Open questions at the time
    • Quantitative contribution of this interaction versus Mg²⁺ coordination not fully deconvoluted
    • Computational transition-state modeling not validated by kinetic isotope effects
  8. 2013 High

    Structural and biophysical evidence showed that M-phase phosphorylation of Ser11 weakens importin-α binding to the DUT-N NLS, providing a cell-cycle switch that excludes dUTPase from the nucleus during mitosis.

    Evidence Crystal structures of importin-α with wild-type and S11E phosphomimetic NLS peptides; ITC; GFP localization with cell-cycle staging

    PMID:24311590

    Open questions at the time
    • Identity of the kinase phosphorylating Ser11 in vivo not established
    • Functional consequence of mitotic nuclear exclusion for dUTP pool partitioning not measured
  9. 2016 High

    Bidirectional manipulation of dUTPase levels in cancer cells placed the enzyme as a critical downstream effector of dNTP pool imbalance caused by ribonucleotide reductase R2 overexpression, with dUTPase overexpression fully suppressing replication stress and genomic uracil accumulation at fragile sites.

    Evidence siRNA knockdown and overexpression in cancer cells; DNA fiber assay, genomic uracil quantification

    PMID:27452458

    Open questions at the time
    • Whether dUTPase acts at replication forks directly or only through bulk pool regulation is unclear
    • In vivo tumor model validation not performed
  10. 2017 High

    Discovery of a homozygous DUT missense mutation (Y142C/Y54C) as the cause of a monogenic syndrome of diabetes and bone marrow failure established dUTPase as essential for human pancreatic β-cell and hematopoietic cell survival, with loss triggering intrinsic apoptosis.

    Evidence Whole-exome sequencing in affected families; siRNA knockdown in human and rat β-cells with apoptosis pathway analysis

    PMID:28073829

    Open questions at the time
    • Structural impact of the Y142C mutation on trimer stability or catalysis not directly characterized
    • Whether bone marrow failure reflects the same apoptotic mechanism as β-cell death not tested
  11. 2018 High

    Characterization of the staphylococcal Stl–human dUTPase complex revealed mutual functional inhibition — Stl binds active-site segments of the dUTPase trimer, blocking catalysis, while dUTPase binding dissociates the Stl homodimer, abolishing its repressor function — illustrating pathogen exploitation of dUTPase surfaces.

    Evidence SAXS, HDX-MS, enzyme kinetics, and DNA binding assays

    PMID:29531348

    Open questions at the time
    • Physiological relevance of human dUTPase–Stl interaction during S. aureus infection not demonstrated
    • Whether other pathogen proteins similarly target human dUTPase is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The kinase responsible for Ser11 phosphorylation in vivo, the structural basis of DUT-N versus DUT-M isoform-specific protein interactions, and the mechanism by which partial dUTPase loss preferentially affects β-cells and hematopoietic cells over other tissues remain open questions.
  • Ser11 kinase identity unknown
  • Tissue-specific vulnerability mechanism unresolved
  • No structural model of disease-associated Y142C mutant trimer

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 6
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-73894 DNA Repair 3 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 1
Partners
KPNA2
Complex memberships
dUTPase homotrimer

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Crystal structure of E. coli dUTPase determined by X-ray crystallography at 1.9 Å resolution; the enzyme is a symmetrical homotrimer with a jelly-roll fold lacking the classical nucleotide-binding domain, and conserved elements cluster at subunit interfaces consistent with a role in catalysis. X-ray crystallography Nature High 1311056
1996 Crystal structure of E. coli dUTPase complexed with substrate analogue dUDP at 1.9 Å revealed three dUDP molecules bound symmetrically per trimer in shallow clefts between adjacent subunits, interacting with evolutionarily conserved residues; interactions of the uracil ring and deoxypentose explain substrate specificity. X-ray crystallography with substrate analogue Nature Structural Biology High 8646539
1996 Kinetic analysis of E. coli dUTPase (closely homologous to human enzyme) showed kcat ~6–9 s⁻¹, Km ~10⁻⁷ M for dUTP·Mg; Mg²⁺ enhances dUTP binding 100-fold; only one enantiomer of α-thio-dUTP is hydrolyzed; proton release is concerted after the rate-limiting step, consistent with a mechanism involving Mg²⁺ binding to α-phosphate and rate-limiting hydrolysis by an activated water molecule. Enzyme kinetics, pH-rate analysis, chiral substrate assay Journal of Biological Chemistry High 8798636
2007 Crystal structure of human dUTPase in complex with α,β-imino-dUTP and Mg²⁺ showed that ordering of the flexible C-terminus upon substrate binding juxtaposes the nucleophile water oxygen and the α-phosphorus below van der Waals distance, enabling catalysis; C-terminus interacts with both substrate and product. X-ray crystallography, equilibrium binding (tryptophan fluorescence sensor) FEBS Letters High 17880943
2007 Pre-steady-state and steady-state kinetic analysis of human dUTPase defined a four-step catalytic cycle: (i) fast substrate binding, (ii) isomerization to catalytically competent conformation, (iii) rate-limiting hydrolysis (chemical step), and (iv) rapid non-ordered product release; proton release is concomitant with the rate-limiting step. Stopped-flow fluorescence, quenched-flow, indicator-based rapid kinetics Journal of Biological Chemistry High 17848562
2013 Phosphorylation of Ser11 on the nuclear isoform of human dUTPase (DUT-N) during M phase weakens its interaction with importin-α, abolishing nuclear import; crystal structures of importin-α bound to wild-type and phosphomimetic (S11E) dUTPase NLS peptides provided structural explanation for this regulation. Crystal structure, ITC, cell biology (GFP fusions, cell-cycle staging), importin-α binding assays Acta Crystallographica Section D High 24311590
2003 The human nuclear dUTPase isoform (DUT-N) contains a monopartite nuclear localization signal (NLS) centered on residues K14R15R17 within its N-terminal 23 amino acids; mutation of these residues completely abolished nuclear localization, whereas phosphorylation of nearby Ser11 had no effect on localization in this assay. GFP fusion constructs, site-directed mutagenesis, fluorescence microscopy Experimental Cell Research Medium 12799180
1993 Human dUTPase is phosphorylated in a cell-cycle-dependent manner in mature T cells (accumulation during proliferation), while immature thymocytes constitutively express both phosphorylated and unphosphorylated forms, indicating proliferation-independent regulation in immature lymphocytes. 2D-PAGE, cDNA cloning, protein identification by partial amino acid sequencing PNAS Medium 8389461
2017 Homozygous missense mutation in DUT (Y142C in DUT-M, Y54C in DUT-N) causes a novel monogenic syndrome with early-onset diabetes and bone marrow failure; DUT silencing in human and rat pancreatic β-cells induces apoptosis via the intrinsic cell death pathway, demonstrating that dUTPase activity is essential for β-cell survival. Whole-exome sequencing, siRNA knockdown, apoptosis assays (flow cytometry, caspase activation) Diabetes High 28073829
2004 siRNA-mediated knockdown of dUTPase in SW620 and MCF-7 cells significantly expanded dUTP pools after thymidylate synthase inhibition, decreased FUdR IC50 (~75-fold in SW620, ~6-fold in MCF-7), reduced clonogenic survival, and enhanced DNA double-strand break formation, establishing that dUTPase opposes uracil misincorporation and drug cytotoxicity. siRNA knockdown, nucleotide pool analysis, clonogenic assay, comet/DSB assays Molecular Pharmacology High 15322254
2016 Reducing dUTPase expression increases genomic uracil content and genome stress in cancer cells; overexpression of dUTPase abolishes ribonucleotide reductase R2-induced genome instability (altered replication fork progression, elevated genomic uracil, breaks at AT-rich fragile sites), placing dUTPase as a key regulator downstream of dNTP pool imbalance. siRNA knockdown, overexpression, DNA fiber assay, genomic uracil quantification, cancer cell models Cell Reports High 27452458
2010 A conserved aromatic stacking interaction between dUTPase and the uracil base of the substrate stabilizes the associative-type transition state of α-phosphate hydrolysis; this remote π-π interaction accelerates catalysis despite the distance from the hydrolysis site, demonstrated by crystallography, kinetics, optical spectroscopy, and thermodynamics calculations. X-ray crystallography, kinetic analysis, optical spectroscopy, thermodynamics (ITC) Nucleic Acids Research High 20601405
2009 The C-terminal β-strand swapping is a principal cohesive force for dUTPase homotrimer assembly; truncation of the C-terminus before the swapping arm prevents trimer formation in human dUTPase, and mutation of a conserved hinge proline destabilizes the enzyme without preventing trimerization. Crystal structure (Drosophila dUTPase dimer), mutagenesis, SAXS, analytical biochemistry FEBS Letters High 19302784
2004 Drosophila dUTPase exists as two isoforms (mRNA and protein level) with differential subcellular localization; immunohistochemistry showed localization does not strictly correlate with presence of a predicted NLS, suggesting additional regulatory factors; macromolecular partners of dUTPase exist in Drosophila cells. Immunohistochemistry, subcellular fractionation, co-immunoprecipitation approaches Journal of Biological Chemistry Medium 14996835
2018 Staphylococcal repressor protein StlSaPIBov1 (Stl) forms a stable complex with human dUTPase trimers; SAXS and HDX-MS showed that active site-forming dUTPase segments are directly involved in the interaction, inhibiting dUTPase enzymatic activity, and that dUTPase binding dissociates the functional Stl homodimer, abolishing its DNA binding capability. SAXS, HDX-MS, enzyme kinetics, functional DNA binding assay Scientific Reports High 29531348
2016 In a mycobacterial model encoding both monofunctional dUTPase (Dut) and bifunctional dCTP deaminase/dUTPase (Dcd:dut), Dut specifically prevents DNA uracilation without affecting dTTP/dCTP balance, while Dcd:dut regulates dNTP balance without preventing DNA uracilation; these two functions of the dUTPase superfamily are thus mechanistically decoupled. Conditional gene knockouts, DNA uracil quantification, dNTP pool analysis, mutation rate measurement Scientific Reports High 28729658
2004 dut mutants in E. coli are synthetically lethal with recA inactivation; the RecBC-RuvABC double-strand break (DSB) repair pathway is required for viability of dut mutants; chromosomal fragmentation (DSBs) was detected in dut rec double mutants; synthetic lethality and chromosomal fragmentation were suppressed by inactivating uracil-DNA glycosylase (ung) or dCTP deaminase (dcd), placing dUTPase upstream of a uracil→nick→DSB→recombinational repair pathway. Genetic epistasis (synthetic lethality screens), pulsed-field gel electrophoresis for DSB detection, SOS induction assays Molecular Microbiology High 14982624

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 Lethality of a dut (deoxyuridine triphosphatase) mutation in Escherichia coli. Journal of bacteriology 182 2830228
1992 Distinct subsets of retroviruses encode dUTPase. Journal of virology 144 1310783
1992 Crystal structure of a dUTPase. Nature 142 1311056
2009 The EBV-encoded dUTPase activates NF-kappa B through the TLR2 and MyD88-dependent signaling pathway. Journal of immunology (Baltimore, Md. : 1950) 132 19124728
1992 Herpes simplex virus type 1 dUTPase mutants are attenuated for neurovirulence, neuroinvasiveness, and reactivation from latency. Journal of virology 128 1328686
2002 Roles of uracil-DNA glycosylase and dUTPase in virus replication. The Journal of general virology 106 12237414
1996 Crystal structure of the Escherichia coli dUTPase in complex with a substrate analogue (dUDP). Nature structural biology 98 8646539
1993 Characterization of equine infectious anemia virus dUTPase: growth properties of a dUTPase-deficient mutant. Journal of virology 97 8386267
2001 The role of dUTPase and uracil-DNA repair in cancer chemotherapy. Current protein & peptide science 96 12374095
1995 Replication in vitro and in vivo of an equine infectious anemia virus mutant deficient in dUTPase activity. Journal of virology 93 7707512
1999 Evolution and horizontal transfer of dUTPase-encoding genes in viruses and their hosts. Journal of virology 91 10438861
1996 Kinetic characterization of dUTPase from Escherichia coli. The Journal of biological chemistry 87 8798636
2006 EBV-encoded dUTPase induces immune dysregulation: Implications for the pathophysiology of EBV-associated disease. Virology 85 16321417
2013 Epstein-Barr virus encoded dUTPase containing exosomes modulate innate and adaptive immune responses in human dendritic cells and peripheral blood mononuclear cells. PloS one 78 23894549
2004 Crystal structure of the Mycobacterium tuberculosis dUTPase: insights into the catalytic mechanism. Journal of molecular biology 78 15276840
1984 Identification of the herpes simplex virus type 1 gene encoding the dUTPase. Virology 77 6149651
1999 African swine fever virus dUTPase is a highly specific enzyme required for efficient replication in swine macrophages. Journal of virology 69 10515998
1997 dUTPase-minus caprine arthritis-encephalitis virus is attenuated for pathogenesis and accumulates G-to-A substitutions. Journal of virology 68 9151845
2004 Chromosomal fragmentation in dUTPase-deficient mutants of Escherichia coli and its recombinational repair. Molecular microbiology 65 14982624
2004 Small interfering RNA-mediated suppression of dUTPase sensitizes cancer cell lines to thymidylate synthase inhibition. Molecular pharmacology 64 15322254
2007 Active site closure facilitates juxtaposition of reactant atoms for initiation of catalysis by human dUTPase. FEBS letters 62 17880943
2017 Pseudorabies Virus dUTPase UL50 Induces Lysosomal Degradation of Type I Interferon Receptor 1 and Antagonizes the Alpha Interferon Response. Journal of virology 61 28794045
2005 New genes from old: redeployment of dUTPase by herpesviruses. Journal of virology 61 16188990
2004 The crystal structure of Trypanosoma cruzi dUTPase reveals a novel dUTP/dUDP binding fold. Structure (London, England : 1993) 60 14725764
2002 Archaeal dUTPase enhances PCR amplifications with archaeal DNA polymerases by preventing dUTP incorporation. Proceedings of the National Academy of Sciences of the United States of America 59 11782527
2015 Exceptional adsorption-induced cluster and network deformation in the flexible metal-organic framework DUT-8(Ni) observed by in situ X-ray diffraction and EXAFS. Physical chemistry chemical physics : PCCP 58 26079102
2008 Active site of mycobacterial dUTPase: structural characteristics and a built-in sensor. Biochemical and biophysical research communications 58 18519027
2007 Kinetic mechanism of human dUTPase, an essential nucleotide pyrophosphatase enzyme. The Journal of biological chemistry 58 17848562
1983 Nucleotide sequence of the structural gene for dUTPase of Escherichia coli K-12. The EMBO journal 54 6139280
1993 Maturation stage and proliferation-dependent expression of dUTPase in human T cells. Proceedings of the National Academy of Sciences of the United States of America 53 8389461
1986 Isolation and characterisation of herpes simplex virus type 1 mutants which fail to induce dUTPase activity. Virology 50 3002029
2011 A human endogenous retrovirus K dUTPase triggers a TH1, TH17 cytokine response: does it have a role in psoriasis? The Journal of investigative dermatology 49 21776007
2006 Acyclic nucleoside analogues as inhibitors of Plasmodium falciparum dUTPase. Journal of medicinal chemistry 49 16821778
2011 The anti-interferon activity of conserved viral dUTPase ORF54 is essential for an effective MHV-68 infection. PLoS pathogens 48 21998588
2011 Inhibition of dUTPase induces synthetic lethality with thymidylate synthase-targeted therapies in non-small cell lung cancer. Molecular cancer therapeutics 48 22172489
2006 Quantitative determination of uracil residues in Escherichia coli DNA: Contribution of ung, dug, and dut genes to uracil avoidance. DNA repair 48 16908222
2012 Kaposi's sarcoma-associated herpesvirus ORF54/dUTPase downregulates a ligand for the NK activating receptor NKp44. Journal of virology 47 22674989
2007 Epstein-Barr virus-encoded dUTPase enhances proinflammatory cytokine production by macrophages in contact with endothelial cells: evidence for depression-induced atherosclerotic risk. Brain, behavior, and immunity 46 17845840
2012 The dUTPase enzyme is essential in Mycobacterium smegmatis. PloS one 45 22655049
2010 Aromatic stacking between nucleobase and enzyme promotes phosphate ester hydrolysis in dUTPase. Nucleic acids research 45 20601405
1993 Vaccinia virus encodes a functional dUTPase. Virology 45 8393252
2019 Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Clinical therapeutics 44 31040055
2015 dUTPase: the frequently overlooked enzyme encoded by many retroviruses. Retrovirology 44 26259899
2002 dUTPase and uracil-DNA glycosylase are central modulators of antifolate toxicity in Saccharomyces cerevisiae. Cancer research 44 12208740
2006 Flexible segments modulate co-folding of dUTPase and nucleocapsid proteins. Nucleic acids research 42 17169987
2000 Deoxyuridine triphosphatase (dUTPase) expression and sensitivity to the thymidylate synthase (TS) inhibitor ZD9331. British journal of cancer 42 10952785
1994 The protein p30, encoded at the gag-pro junction of mouse mammary tumor virus, is a dUTPase fused with a nucleocapsid protein. Virology 40 8091672
2000 The non-essential UL50 gene of avian infectious laryngotracheitis virus encodes a functional dUTPase which is not a virulence factor. The Journal of general virology 39 10675400
2001 Kinetic properties and inhibition of the dimeric dUTPase-dUDPase from Leishmania major. Protein science : a publication of the Protein Society 36 11420444
2021 Monocyte-released HERV-K dUTPase engages TLR4 and MCAM causing endothelial mesenchymal transition. JCI insight 35 34185707
2006 Characterization of an early gene encoding for dUTPase in Rana grylio virus. Virus research 35 16989917
2004 Developmental regulation of dUTPase in Drosophila melanogaster. The Journal of biological chemistry 35 14996835
1999 Structure/function analysis of a dUTPase: catalytic mechanism of a potential chemotherapeutic target. Journal of molecular biology 35 10329142
1990 Cell cycle- and differentiation stage-dependent variation of dUTPase activity in higher plant cells. Experimental cell research 34 2153555
2013 Phosphorylation adjacent to the nuclear localization signal of human dUTPase abolishes nuclear import: structural and mechanistic insights. Acta crystallographica. Section D, Biological crystallography 33 24311590
1998 Biochemical and phylogenetic characterization of the dUTPase from the archaeal virus SIRV. The Journal of biological chemistry 33 9497317
1996 Identification and characterization of pseudorabies virus dUTPase. Journal of virology 33 8551588
2019 Crystal Structure of African Swine Fever Virus dUTPase Reveals a Potential Drug Target. mBio 32 31662460
2017 dUTPase inhibition augments replication defects of 5-Fluorouracil. Oncotarget 32 28423595
2008 Methylene substitution at the alpha-beta bridging position within the phosphate chain of dUDP profoundly perturbs ligand accommodation into the dUTPase active site. Proteins 30 17932923
2008 Genome analysis of small-ruminant lentivirus genotype E: a caprine lentivirus with natural deletions of the dUTPase subunit, vpr-like accessory gene, and 70-base-pair repeat of the U3 region. Journal of virology 30 18987157
2007 Mechanism of dTTP inhibition of the bifunctional dCTP deaminase:dUTPase encoded by Mycobacterium tuberculosis. Journal of molecular biology 30 18164314
1997 Study of immunogenicity and virulence of bovine herpesvirus 1 mutants deficient in the UL49 homolog, UL49.5 homolog and dUTPase genes in cattle. Vaccine 30 9269047
1993 dUTPase from herpes simplex virus type 1; purification from infected green monkey kidney (Vero) cells and from an overproducing Escherichia coli strain. Protein expression and purification 29 8386036
2008 Synthetic lethality with the dut defect in Escherichia coli reveals layers of DNA damage of increasing complexity due to uracil incorporation. Journal of bacteriology 28 18586941
2016 Life without dUTPase. Frontiers in microbiology 27 27933035
2013 Phosphorylation of a herpes simplex virus 1 dUTPase by a viral protein kinase, Us3, dictates viral pathogenicity in the central nervous system but not at the periphery. Journal of virology 27 24352467
2001 Atomic resolution structure of Escherichia coli dUTPase determined ab initio. Acta crystallographica. Section D, Biological crystallography 27 11375495
2001 Evolution of the DUT gene: horizontal transfer between host and pathogen in all three domains of life. Current protein & peptide science 27 12369928
2020 dUTPase inhibition confers susceptibility to a thymidylate synthase inhibitor in DNA-repair-defective human cancer cells. Cancer science 26 33140501
2005 Haplotype sharing analysis identifies a retroviral dUTPase as candidate susceptibility gene for psoriasis. The Journal of investigative dermatology 26 15654959
1997 Characterization and mutational studies of equine infectious anemia virus dUTPase. Biochimica et biophysica acta 26 9187238
1996 Synthesis of 2'-deoxyuridine 5'-(alpha,beta-imido) triphosphate: a substrate analogue and potent inhibitor of dUTPase. Bioorganic & medicinal chemistry 26 8735843
2008 The action of Pdcd4 may be cell type specific: evidence that reduction of dUTPase levels might contribute to its tumor suppressor activity in Bon-1 cells. Apoptosis : an international journal on programmed cell death 25 17955371
2003 Structural basis for recognition and catalysis by the bifunctional dCTP deaminase and dUTPase from Methanococcus jannaschii. Journal of molecular biology 25 12909016
2018 TAS-114, a First-in-Class Dual dUTPase/DPD Inhibitor, Demonstrates Potential to Improve Therapeutic Efficacy of Fluoropyrimidine-Based Chemotherapy. Molecular cancer therapeutics 24 29748212
2016 The nucleotidohydrolases DCTPP1 and dUTPase are involved in the cellular response to decitabine. The Biochemical journal 24 27325794
2016 The Impact of dUTPase on Ribonucleotide Reductase-Induced Genome Instability in Cancer Cells. Cell reports 24 27452458
2001 Evolution of the dUTPase gene of mammalian and avian herpesviruses. Current protein & peptide science 24 12369929
2013 Structure and enzymatic mechanism of a moonlighting dUTPase. Acta crystallographica. Section D, Biological crystallography 23 24311572
2011 β-Branched acyclic nucleoside analogues as inhibitors of Plasmodium falciparum dUTPase. Bioorganic & medicinal chemistry 23 21411327
2009 Molecular shape and prominent role of beta-strand swapping in organization of dUTPase oligomers. FEBS letters 23 19302784
2008 Identification and characterization of duck enteritis virus dUTPase gene. Avian diseases 23 18646465
2008 Higher expression of deoxyuridine triphosphatase (dUTPase) may predict the metastasis potential of colorectal cancer. Journal of clinical pathology 23 19052026
2004 Evidence that the human cytomegalovirus 46-kDa UL72 protein is not an active dUTPase but a late protein dispensable for replication in fibroblasts. Virology 23 15246266
2011 Molecular modeling of Mycobacterium tuberculosis dUTpase: docking and catalytic mechanism studies. Journal of biomolecular structure & dynamics 22 21469751
1997 A consensus sequence for a functional human endogenous retrovirus K (HERV-K) dUTPase. Biochemistry and cell biology = Biochimie et biologie cellulaire 22 9250362
1995 dUTPase from the retrovirus equine infectious anemia virus: high-level expression in Escherichia coli and purification. Protein expression and purification 22 7663176
2018 Structural model of human dUTPase in complex with a novel proteinaceous inhibitor. Scientific reports 21 29531348
2017 dUTPase (DUT) Is Mutated in a Novel Monogenic Syndrome With Diabetes and Bone Marrow Failure. Diabetes 21 28073829
2017 Differential control of dNTP biosynthesis and genome integrity maintenance by the dUTPase superfamily enzymes. Scientific reports 21 28729658
2015 Cross-species inhibition of dUTPase via the Staphylococcal Stl protein perturbs dNTP pool and colony formation in Mycobacterium. DNA repair 21 25841100
2012 Protective effect of human endogenous retrovirus K dUTPase variants on psoriasis susceptibility. The Journal of investigative dermatology 21 22437317
2011 Homologous recombination is stimulated by a decrease in dUTPase in Arabidopsis. PloS one 21 21541310
2003 Identification of sequence determinants of human nuclear dUTPase isoform localization. Experimental cell research 21 12799180
1998 Visna virus dUTPase is dispensable for neuropathogenicity. Journal of virology 21 9445073
1997 Attenuation of dUTPase-deficient pseudorabies virus for the natural host. Veterinary microbiology 21 9228681
2014 Phosphorylation of herpes simplex virus 1 dUTPase upregulated viral dUTPase activity to compensate for low cellular dUTPase activity for efficient viral replication. Journal of virology 20 24760895
2007 Structures of vaccinia virus dUTPase and its nucleotide complexes. Acta crystallographica. Section D, Biological crystallography 20 17452782
2003 Structure of the bifunctional dCTP deaminase-dUTPase from Methanocaldococcus jannaschii and its relation to other homotrimeric dUTPases. The Journal of biological chemistry 20 12756253