Antibiotic resistance is a global concern. Two members of the bacterial genus namely, and have raised much concern in recent years because of their resistance to multiple commonly used antibiotics. Identification of multidrug resistant and pan-drug resistant bacteria has propelled the search for new antibiotics that can act on unconventional targets. Researches are going on to find out the possibility of using bacterial ribonucleotide reductases as a novel target for antibiotic development. Through evaluations, this study aims for characterization and functional annotation of ribonucleotide reductase enzymes of and . Binding affinities with these enzymes of the compounds that have shown promising results in inhibiting growth by acting on its ribonucleotide reductase were also assessed by molecular docking and dynamics simulations. Insights from this study will help in battling these infections in the near future. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2021.1930166 | DOI Listing |
In Saccharomyces cerevisiae cells, the bulk of mitochondrial DNA (mtDNA) replication is mediated by the replicative high-fidelity DNA polymerase γ. However, upon UV irradiation low-fidelity translesion polymerases: Polη, Polζ and Rev1, participate in an error-free replicative bypass of UV-induced lesions in mtDNA. We analysed how translesion polymerases could function in mitochondria.
View Article and Find Full Text PDFInt J Biol Sci
December 2024
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Tyrosine kinase inhibitors (TKIs), such as sunitinib, have emerged as promising agents in renal cell carcinoma (RCC) treatment, particularly in patients at advanced/metastatic clinical stages. However, acquired resistance to sunitinib is common following prolonged clinical treatment in RCC. Increasing evidence has demonstrated a strong correlation between inhibitor of nuclear factor kappa B kinase subunit epsilon (IKBKE) and cancer progression as well as drug resistance.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
November 2024
Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Disease, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China.
DNA replication stress is a significant contributor to spontaneous DNA damage and genome instability. While the impact of p53 deficiency on increasing DNA replication stress is known, the specific molecular mechanism underlying this phenomenon remains poorly understood. This study explores how p53 deficiency induces DNA replication stress by activating mTORC1 through R-loop formation, which is facilitated by the upregulation of RNR.
View Article and Find Full Text PDFEur J Pharm Sci
January 2025
Department of Oriental Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, South Korea. Electronic address:
A highly aggressive neoplastic disease, pancreatic ductal adenocarcinoma (PDAC) is documented as the third chief cause of cancer-associated mortality in both sexes combined in the United States. For decades, gemcitabine-based chemotherapy has been embraced as a cornerstone drug for the treatment of PDAC. However, there have been several unsolved problems, including cytotoxicity, and chemoresistance.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States.
The enzyme ribonucleotide reductase plays a critical role in DNA synthesis and repair. Its mechanism requires long-range radical transfer through a series of proton-coupled electron transfer (PCET) steps. Nuclear quantum effects such as zero-point energy, proton delocalization, and hydrogen tunneling are known to be important in PCET.
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