ArticleProceedings of the National Academy of Sciences of the United States of America2006
Structures of eukaryotic ribonucleotide reductase I define gemcitabine diphosphate binding and subunit assembly.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 70 citations in OpenAlex.
- Induced DNA double strand breaks by genotoxic drugs occur at active transcription H3K36 tri-methylation sites.Communications biology · 2026Article
- Targeting replication stress in neuroblastoma by exploiting the synergistic potential of second generation RRM2 and CHK1 inhibitors.Cell death & disease · 2026Article
- Efficacy of Chemotherapy Following Prior PARP-Inhibitor Treatment in Patients with Ovarian Cancer.Cancer research and treatment · 2026Article
- How ATP and dATP reposition class III ribonucleotide reductase cone domains to regulate enzyme activity.Science advances · 2025Article
- Ribonucleotide reductase (RNR) inhibitors as target-based weapon for future cancer drug development.Future medicinal chemistry · 2025Review
- αβ,α'β'-Diepoxyketones are mechanism-based inhibitors of nucleophilic cysteine enzymes.Chemical communications (Cambridge, England) · 2023Article
- A missense mutation in themicroPublication biology · 2023Article
- Advances in covalent drug discovery.Nature reviews. Drug discovery · 2022Review
- Tunable Cysteine-Targeting Electrophilic Heteroaromatic Warheads Induce Ferroptosis.Journal of medicinal chemistry · 2022Article
- Inhibitors of the Cancer Target Ribonucleotide Reductase, Past and Present.Biomolecules · 2022Review
- Structural and Biochemical Investigation of Class I Ribonucleotide Reductase from the HyperthermophileBiochemistry · 2022Article
- Human pyrimidine nucleotide biosynthesis as a target for antiviral chemotherapy.Current opinion in biotechnology · 2017Review
- Potent competitive inhibition of human ribonucleotide reductase by a nonnucleoside small molecule.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Quantitative Structure-Cytotoxic Activity Relationship 1-(Benzoyloxy)urea and Its Derivative.Current drug discovery technologies · 2016Article
- Hug1 is an intrinsically disordered protein that inhibits ribonucleotide reductase activity by directly binding Rnr2 subunit.Nucleic acids research · 2014Article
- The structural basis for the allosteric regulation of ribonucleotide reductase.Progress in molecular biology and translational science · 2013Review
- Evaluating the therapeutic potential of a non-natural nucleotide that inhibits human ribonucleotide reductase.Molecular cancer therapeutics · 2012Article
- Role of arginine 293 and glutamine 288 in communication between catalytic and allosteric sites in yeast ribonucleotide reductase.Journal of molecular biology · 2012Article
- Targeting the Large Subunit of Human Ribonucleotide Reductase for Cancer Chemotherapy.Pharmaceuticals (Basel, Switzerland) · 2011Article
- The resurgence of covalent drugs.Nature reviews. Drug discovery · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Ribonucleotide reductase (RNR) catalyzes the conversion of nucleoside diphosphates to deoxynucleoside diphosphates. Crucial for rapidly dividing cells, RNR is a target for cancer therapy. In eukaryotes, RNR comprises a heterooligomer of alpha(2) and beta(2) subunits. Rnr1, the alpha subunit, contains regulatory and catalytic sites; Rnr2, the beta subunit (in yeast, a heterodimer of Rnr2 and Rnr4), houses the diferric-tyrosyl radical crucial for catalysis. Here, we present three x-ray structures of eukaryotic Rnr1 from Saccharomyces cerevisiae: one bound to gemcitabine diphosphate (GemdP), the active metabolite of the mechanism-based chemotherapeutic agent gemcitabine; one with an Rnr2-derived peptide, and one with an Rnr4-derived peptide. Our structures reveal that GemdP binds differently from its analogue, cytidine diphosphate; because of unusual interactions of the geminal fluorines, the ribose and base of GemdP shift substantially, and loop 2, which mediates substrate specificity, adopts different conformations when binding to GemdP and cytidine diphosphate. The Rnr2 and Rnr4 peptides, which block RNR assembly, bind differently from each other but have unique modes of binding not seen in prokaryotic RNR. The Rnr2 peptide adopts a conformation similar to that previously reported from an NMR study for a mouse Rnr2-based peptide. In yeast, the Rnr2 peptide binds at subsites consisting of residues that are highly conserved among yeast, mouse, and human Rnr1s, suggesting that the mode of Rnr1-Rnr2 binding is conserved among eukaryotes. These structures provide new insights into subunit assembly and a framework for structure-based drug design targeting RNR.
Indexed as
Identifiers
What OpenQuestion holds
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.