ArticleNucleic acids research2010
Aromatic stacking between nucleobase and enzyme promotes phosphate ester hydrolysis in dUTPase.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 62 citations in OpenAlex.
- Targeting opportunities presented by the pyrimidine biosynthesis pathway in Mycobacterium tuberculosis: a brief review.Biochemical Society transactions · 2026Review
- GC-MS analysis, molecular docking, and pharmacokinetic studies on Dalbergia sissoo barks extracts for compounds with anti-diabetic potential.Scientific reports · 2024Article
- Pharmacological basis of bergapten in gastrointestinal diseases focusing on HFrontiers in pharmacology · 2022Article
- In Vitro Evaluation of the Anti-Diabetic Potential of Aqueous AcetoneMolecules (Basel, Switzerland) · 2021Article
- Redox status of cysteines does not alter functional properties of human dUTPase but the Y54C mutation involved in monogenic diabetes decreases protein stability.Scientific reports · 2021Article
- NF-κB Inhibitors Attenuate MCAO Induced Neurodegeneration and Oxidative Stress-A Reprofiling Approach.Frontiers in molecular neuroscience · 2020Article
- Computational and Pharmacological Evaluation of Carveol for Antidiabetic Potential.Frontiers in pharmacology · 2020Article
- Beyond Chelation: EDTA Tightly Binds Taq DNA Polymerase, MutT and dUTPase and Directly Inhibits dNTPase Activity.Biomolecules · 2019Article
- The Role of a Key Amino Acid Position in Species-Specific Proteinaceous dUTPase Inhibition.Biomolecules · 2019Article
- Enzyme kinetics of dUTPase from the planarian Dugesia ryukyuensis.BMC research notes · 2019Article
- Structural model of human dUTPase in complex with a novel proteinaceous inhibitor.Scientific reports · 2018Article
- Differential control of dNTP biosynthesis and genome integrity maintenance by the dUTPase superfamily enzymes.Scientific reports · 2017Article
- Computational and Pharmacological Evaluation of Ferrocene-Based Acyl Ureas and Homoleptic Cadmium Carboxylate Derivatives for Anti-diabetic Potential.Frontiers in pharmacology · 2017Article
- A Hidden Active Site in the Potential Drug Target Mycobacterium tuberculosis dUTPase Is Accessible through Small Amplitude Protein Conformational Changes.The Journal of biological chemistry · 2016Article
- Another look at the mechanism involving trimeric dUTPases in Staphylococcus aureus pathogenicity island induction involves novel players in the party.Nucleic acids research · 2016Article
- Trading in cooperativity for specificity to maintain uracil-free DNA.Scientific reports · 2016Article
- Structural insights into the mechanism defining substrate affinity in Arabidopsis thaliana dUTPase: the role of tryptophan 93 in ligand orientation.BMC research notes · 2015Article
- Evidence-Based Structural Model of the Staphylococcal Repressor Protein: Separation of Functions into Different Domains.PloS one · 2015Article
- 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.Nucleic acids research · 2013Article
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Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Aromatic interactions are well-known players in molecular recognition but their catalytic role in biological systems is less documented. Here, we report that a conserved aromatic stacking interaction between dUTPase and its nucleotide substrate largely contributes to the stabilization of the associative type transition state of the nucleotide hydrolysis reaction. The effect of the aromatic stacking on catalysis is peculiar in that uracil, the aromatic moiety influenced by the aromatic interaction is relatively distant from the site of hydrolysis at the alpha-phosphate group. Using crystallographic, kinetics, optical spectroscopy and thermodynamics calculation approaches we delineate a possible mechanism by which rate acceleration is achieved through the remote π-π interaction. The abundance of similarly positioned aromatic interactions in various nucleotide hydrolyzing enzymes (e.g. most families of ATPases) raises the possibility of the reported phenomenon being a general component of the enzymatic catalysis of phosphate ester hydrolysis.
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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.