Dual-Specificity Phosphatase CDC25B Was Inhibited by Natural Product HB-21 Through Covalently Binding to the Active Site

Zhang, Shoude; Jia, Qiangqiang; Gao, Qiang; Fan, Xueru; Weng, Yuxin; Su, Zhanhai

doi:10.3389/fchem.2018.00531

Cited by 9 publications

(5 citation statements)

References 23 publications

(32 reference statements)

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“…Refinement statistics are listed in tableS1. Protein-RNA contacts were determined from PDB 6ff4 of the human B act structure using the contact program from the CCP4 suite(46), and then extracting the unique contacts of core proteins with U2 and U6 snRNA.…”

mentioning

confidence: 99%

Mechanism of protein-guided folding of the active site U2/U6 RNA during spliceosome activation

Townsend

Leelaram

Agafonov

et al. 2020

Science

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Spliceosome activation involves extensive protein and RNA rearrangements that lead to formation of a catalytically-active U2/U6 RNA structure. At present, little is known about the assembly pathway of the latter and the mechanism whereby proteins aid its proper folding. Here we report the cryo-electron microscopy structures of two human pre-Bact complexes at core resolutions of 3.9-4.2 Å. These structures elucidate the order of the numerous protein exchanges that occur during activation, the mutually-exclusive interactions that ensure the correct order of ribonucleoprotein rearrangements needed to form the U2/U6 catalytic RNA, and the stepwise folding pathway of the latter. Structural comparisons with mature Bact complexes reveal the molecular mechanism whereby a conformational change in the scaffold protein PRP8 facilitates final 3D folding of the U2/U6 catalytic RNA.

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confidence: 99%

Mechanism of protein-guided folding of the active site U2/U6 RNA during spliceosome activation

Townsend

Leelaram

Agafonov

et al. 2020

Science

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“…Thus, CDC25A might serve as a potential therapeutic target in breast cancer ( 247 ). One of the compounds that has an inhibitory effect towards CDC25A/B is an o-hydroxybenzyl derivative RE44 (10d), which has shown promise in models of mouse tsFT210 breast cancer cell line in vivo ( 172 , 173 ) ( Table 2 ).…”

Section: Other Proteinsmentioning

confidence: 99%

Centrosomes and associated proteins in pathogenesis and treatment of breast cancer

Athwal,

Kochiyanil,

Bhat

et al. 2024

Front. Oncol.

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Breast cancer is the most prevalent malignancy among women worldwide. Despite significant advances in treatment, it remains one of the leading causes of female mortality. The inability to effectively treat advanced and/or treatment-resistant breast cancer demonstrates the need to develop novel treatment strategies and targeted therapies. Centrosomes and their associated proteins have been shown to play key roles in the pathogenesis of breast cancer and thus represent promising targets for drug and biomarker development. Centrosomes are fundamental cellular structures in the mammalian cell that are responsible for error-free execution of cell division. Centrosome amplification and aberrant expression of its associated proteins such as Polo-like kinases (PLKs), Aurora kinases (AURKs) and Cyclin-dependent kinases (CDKs) have been observed in various cancers, including breast cancer. These aberrations in breast cancer are thought to cause improper chromosomal segregation during mitosis, leading to chromosomal instability and uncontrolled cell division, allowing cancer cells to acquire new genetic changes that result in evasion of cell death and the promotion of tumor formation. Various chemical compounds developed against PLKs and AURKs have shown meaningful antitumorigenic effects in breast cancer cells in vitro and in vivo. The mechanism of action of these inhibitors is likely related to exacerbation of numerical genomic instability, such as aneuploidy or polyploidy. Furthermore, growing evidence demonstrates enhanced antitumorigenic effects when inhibitors specific to centrosome-associated proteins are used in combination with either radiation or chemotherapy drugs in breast cancer. This review focuses on the current knowledge regarding the roles of centrosome and centrosome-associated proteins in breast cancer pathogenesis and their utility as novel targets for breast cancer treatment.

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“…Another key enzyme namely, dual specificity phosphatases (DUSP) [CDC25A, CDC25B and CDC25C] are the enzymes that regulate phosphorylation of cyclin-dependent kinases (substrates) during the cell cycle progression. In contrast, (i) cancer, (ii) diabetes, and (iii) neurodegenerative disorders have been associated with dysregulation of DUSP activity [ 3 ]. Therefore, identifying natural compounds that inhibit DUSP activity has been reported to possess therapeutically uses.…”

Section: Introductionmentioning

confidence: 99%

Molecular Docking Analysis of Selected Urtica dioica Constituents As Human Carbonic Anhydrase II (hCA-II), Human 11 Beta-Hydroxysteroid Dehydrogenases Type 1 (h11beta-HSD1), and Human Dual Specificity Phosphatase (hCDC25B) Inhibitory Agents

Arulselvan,

Manimuthu,

Narayanaswamy

2024

Cureus

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Background Urtica dioica (Stinging nettle)has been reported to exhibit various pharmacological activities. In the present study, we aimed to evaluate 24 selected constituents of U. dioica as potent inhibitory agents of human carbonic anhydrase II (hCA-II), human 11 beta-hydroxysteroid dehydrogenases type 1 (h11beta-HSD1), and human dual specificity phosphatase (hCDC25B) using in silico method. Methodology The 24 selected constituents of U. dioica (Stinging nettle) were studied on the docking behavior of hCA-II, h11beta-HSD1, and hCDC25B by using the Webina docking method. In addition to docking, toxicity analysis was also performed using the pkCSM free web server, respectively. Results Toxicity analysis has shown that six ligands (25%) of U. dioica (Stinging nettle) are predicted to have hERG II (Human ether-a-go-go-related gene) inhibition activity. The docking analysis showed that afzelin, stigmastane-3, 6-diol, and astragalin of U. dioica have shown the maximum binding energy (-7.2, -9.5, and -8.5 kcal/mol) with the hCA-II, h11beta-HSD1 and hCDC25B, respectively. Conclusions Thus, the current finding provides new knowledge about the 24 selected ligands of U. dioica (Stinging nettle) as potent inhibitory agents of human carbonic anhydrase II (hCA-II), human 11 beta-hydroxysteroid dehydrogenases type 1 (h11beta-HSD1) and human dual specificity phosphatase (hCDC25B).

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Dual-Specificity Phosphatase CDC25B Was Inhibited by Natural Product HB-21 Through Covalently Binding to the Active Site

Cited by 9 publications

References 23 publications

Mechanism of protein-guided folding of the active site U2/U6 RNA during spliceosome activation

Mechanism of protein-guided folding of the active site U2/U6 RNA during spliceosome activation

Centrosomes and associated proteins in pathogenesis and treatment of breast cancer

Molecular Docking Analysis of Selected Urtica dioica Constituents As Human Carbonic Anhydrase II (hCA-II), Human 11 Beta-Hydroxysteroid Dehydrogenases Type 1 (h11beta-HSD1), and Human Dual Specificity Phosphatase (hCDC25B) Inhibitory Agents

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