ArticleNucleic acids research2013
Catalytic mechanism of α-phosphate attack in dUTPase is revealed by X-ray crystallographic snapshots of distinct intermediates, 31P-NMR spectroscopy and reaction path modelling.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Structural dynamics of human deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase).Scientific reports · 2024Article
- Systematic QM/MM Study for PredictingJournal of chemical theory and computation · 2024Article
- Catalytic mechanism of the colistin resistance protein MCR-1.Organic & biomolecular chemistry · 2021Article
- Beyond Chelation: EDTA Tightly Binds Taq DNA Polymerase, MutT and dUTPase and Directly Inhibits dNTPase Activity.Biomolecules · 2019Article
- The structure of a polygamous repressor reveals how phage-inducible chromosomal islands spread in nature.Nature communications · 2019Article
- The Stl repressor fromFEBS open bio · 2018Article
- Structural insights into the mechanism defining substrate affinity in Arabidopsis thaliana dUTPase: the role of tryptophan 93 in ligand orientation.BMC research notes · 2015Article
- Cooperative Electrostatic Interactions Drive Functional Evolution in the Alkaline Phosphatase Superfamily.Journal of the American Chemical Society · 2015Article
- Structural snapshots illustrate the catalytic cycle of β-galactocerebrosidase, the defective enzyme in Krabbe disease.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
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11 authors.
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Abstract
Enzymatic synthesis and hydrolysis of nucleoside phosphate compounds play a key role in various biological pathways, like signal transduction, DNA synthesis and metabolism. Although these processes have been studied extensively, numerous key issues regarding the chemical pathway and atomic movements remain open for many enzymatic reactions. Here, using the Mason-Pfizer monkey retrovirus dUTPase, we study the dUTPase-catalyzed hydrolysis of dUTP, an incorrect DNA building block, to elaborate the mechanistic details at high resolution. Combining mass spectrometry analysis of the dUTPase-catalyzed reaction carried out in and quantum mechanics/molecular mechanics (QM/MM) simulation, we show that the nucleophilic attack occurs at the α-phosphate site. Phosphorus-31 NMR spectroscopy ((31)P-NMR) analysis confirms the site of attack and shows the capability of dUTPase to cleave the dUTP analogue α,β-imido-dUTP, containing the imido linkage usually regarded to be non-hydrolyzable. We present numerous X-ray crystal structures of distinct dUTPase and nucleoside phosphate complexes, which report on the progress of the chemical reaction along the reaction coordinate. The presently used combination of diverse structural methods reveals details of the nucleophilic attack and identifies a novel enzyme-product complex structure.
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