Herein we present a multidisciplinary discussion of ribonucleotide reductase (RNR), the essential enzyme uniquely responsible for conversion of ribonucleotides to deoxyribonucleotides. This chapter primarily presents an overview of this multifaceted and complex enzyme, covering RNR's role in enzymology, biochemistry, medicinal chemistry, and cell biology. It further focuses on RNR from mammals, whose interesting and often conflicting roles in health and disease are coming more into focus. We present pitfalls that we think have not always been dealt with by researchers in each area and further seek to unite some of the field-specific observations surrounding this enzyme. Our work is thus not intended to cover any one topic in extreme detail, but rather give what we consider to be the necessary broad grounding to understand this critical enzyme holistically. Although this is an approach we have advocated in many different areas of scientific research, there is arguably no other single enzyme that embodies the need for such broad study than RNR. Thus, we submit that RNR itself is a paradigm of interdisciplinary research that is of interest from the perspective of the generalist and the specialist alike. We hope that the discussions herein will thus be helpful to not only those wanting to tackle RNR-specific problems, but also those working on similar interdisciplinary projects centering around other enzymes.
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http://dx.doi.org/10.1007/978-3-031-00793-4_5 | DOI Listing |
Innate immune response cells produce high concentrations of the free radical nitric oxide (NO) in response to pathogen infection. The antimicrobial properties of NO include non-specific damage to essential biomolecules and specific inactivation of enzymes central to aerobic metabolism. However, the molecular targets of NO in anaerobic metabolism are less understood.
View Article and Find Full Text PDFPLoS One
March 2025
Research Department, KM Biologics Co., Ltd., Kikuchi, Kumamoto, Japan.
To generate a novel oncolytic vaccinia virus with improved safety and productivity, the genome of smallpox vaccine strain LC16m8 was modified by a bacterial artificial chromosome system. By using LC16m8, a replicating virus homologous to the target virus, as a helper virus for the bacterial artificial chromosome system, we successfully recovered genome-edited infectious viruses. Oncolytic viruses with limited growth in normal cells were obtained by deleting the genes for vaccinia virus growth factor (VGF), extracellular signal-regulated kinase-activating protein (O1L), and ribonucleotide reductase (RNR) present in the viral genome.
View Article and Find Full Text PDFFEBS J
March 2025
Biochemistry & Structural Biology, Centre for Molecular Protein Science, Department of Chemistry, Lund University, Sweden.
NrdR is a bacterial transcriptional repressor consisting of a zinc (Zn)-ribbon domain followed by an ATP-cone domain. Understanding its mechanism of action could aid the design of novel antibacterials. NrdR binds specifically to two "NrdR boxes" upstream of ribonucleotide reductase operons, of which Escherichia coli has three: nrdHIEF, nrdDG and nrdAB, in the last of which we identified a new box.
View Article and Find Full Text PDFBiomolecules
February 2025
Université Paris Cité, CNRS, Institut Jacques Monod, 75013 Paris, France.
The has guided the way experiments into DNA replication have been designed and interpreted for 60 years. As part of the related, explanatory package guiding experiments, it is thought that the timing of the cell cycle depends in some way on a critical mass for initiation, , as licensed by a variety of macromolecules and molecules reflecting the state of the cell. To help in the re-interpretation of this data, we focus mainly on the roles of DnaA, RNA polymerase, SeqA, and ribonucleotide reductase in the context of the "nucleotypic effect".
View Article and Find Full Text PDFCommun Biol
February 2025
Department of Biochemistry and Biophysics, Stockholm University, Arrhenius Laboratories for Natural Sciences, Stockholm, Sweden.
Class I ribonucleotide reductases (RNRs) convert ribonucleotides into deoxyribonucleotides under oxic conditions. The R2 subunit provides a radical required for catalysis conducted by the R1 subunit. In most R2s the radical is generated on a tyrosine via oxidation by an adjacent metal site.
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