Two intermediate states of the conformational switch in dual specificity phosphatase 13a

Wei, Chun Hwa; Min, Hee Gyeong; Kim, Myeongbin; Kim, Gwan Hee; Chun, Hyunaee; Ryu, Seong Eon

doi:10.1016/j.phrs.2017.10.006

Cited by 3 publications

(2 citation statements)

References 35 publications

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“…The energy-minimized three-dimensional structure of BCI was procured from the NCBI PubChem database. The prepared ligand was computationally screened against calcium sensing receptor (CASR) (PDB ID: 7dtt) [ 21 ], C-X-C chemokine receptor type 3 (CXCR3) (PDB ID: 6wzk) [ 22 ], cyclin-dependent kinase-5 (CDK5) (PDB ID: 1unl) [ 23 ], cathepsin D (CPSD) (PDB ID: 4od9) [ 24 ], casein kinase II subunit alpha (CK2A1) (PDB ID: 6tls) [ 25 ], cyclin-dependent kinase-1 (CDK1) (PDB ID: 6gu2) [ 26 ], dopamine D1 receptor (DRD1) (PDB ID: 7ckx) [ 27 ], dual specificity phosphatase 13a (DUSP13) (PDB ID: 5xjv) [ 28 ], dual specificity phosphatase 14 (DUSP14) (PDB ID: 2wgp) [ 29 ], dual specificity phosphatase 18 (DUSP18) (PDB ID: 2esb) [ 30 ], dual specificity phosphatase 2 (DUSP2) (PDB ID: 1m3g) [ 31 ], dual specificity phosphatase 28 (DUSP28) (PDB ID: 5y15) [ 32 ], dual specificity phosphatase 5 (DUSP5) (PDB ID: 2g6z) [ 33 ], dual specificity phosphatase 6 (DUSP6) (PDB ID: 1hzm) [ 34 ], dual specificity phosphatase 7 (DUPS7) (PDB ID: 4y2e) [ 35 ], dual specificity phosphatase 8 (DUSP8) (PDB ID: 4jmk) [ 36 ], dipeptidyl peptidase IV (DPP4) (PDB ID: 4pv7) [ 37 ], glucagon-like peptide-1 receptor (GLP-1R) (PDB ID: 5vai) [ 38 ], human apurinic/apyrimidinic endonuclease 1 (APE1) (PDB ID: 6bow) [ 39 ], human indoleamine 2,3-dioxygenase-1 (IDO1) (PDB ID: 6e43) [ 40 ], human topoisomerase-II beta (TOP2β) (PDB ID: 3qx3) [ 41 ], intercellular adhesion molecule (ICAM-1) (PDB ID: 5mza) [ 42 ], lysosomal pro-X carboxypeptidase (PRCP) (PDB ID: 3n2z) [ 43 ], Mu opioid receptor (OPRM1) (PDB ID: 4dkl) [ 44 ], plasminogen activator inhibitor type-1 (PAI-1) (PDB ID: 3cvm) [ 45 ], rho-associated protein kinase-1 (ROCK1) (PDB ID: 3v8s) [ 46 ], rho-associated protein kinase-2 (ROCK2) (PDB ID: 6ed6) [ 47 ], serotonin 5a (5-HT5a) receptor (PDB ID: 7x5h) [ 48 ], signal transducer and activator of transcription-3 (STAT3) (PDB ID: 6nuq) [ 49 ], somatostatin receptor 3 (SSTR3) (PDB ID: 7xms) [ 50 ], tripartite motif-containing 24 ...…”

Section: Methodsmentioning

confidence: 99%

In Vitro and In Silico Investigation of BCI Anticancer Properties and Its Potential for Chemotherapy-Combined Treatments

Marciniak,

Kciuk,

Mujwar

et al. 2023

Cancers

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Background: DUSP6 phosphatase serves as a negative regulator of MAPK kinases involved in numerous cellular processes. BCI has been identified as a potential allosteric inhibitor with anticancer activity. Our study was designed to test the anticancer properties of BCI in colon cancer cells, to characterize the effect of this compound on chemotherapeutics such as irinotecan and oxaliplatin activity, and to identify potential molecular targets for this inhibitor. Methods: BCI cytotoxicity, proapoptotic activity, and cell cycle distribution were investigated in vitro on three colon cancer cell lines (DLD1, HT-29, and Caco-2). In silico investigation was prepared to assess BCI drug-likeness and identify potential molecular targets. Results: The exposure of colorectal cancer cells with BCI resulted in antitumor effects associated with cell cycle arrest and induction of apoptosis. BCI exhibited strong cytotoxicity on DLD1, HT-29, and Caco-2 cells. BCI showed no significant interaction with irinotecan, but strongly attenuated the anticancer activity of oxaliplatin when administered together. Analysis of synergy potential further confirmed the antagonistic interaction between these two compounds. In silico investigation indicated CDK5 as a potential new target of BCI. Conclusions: Our studies point to the anticancer potential of BCI but note the need for a precise mechanism of action.

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Section: Methodsmentioning

confidence: 99%

In Vitro and In Silico Investigation of BCI Anticancer Properties and Its Potential for Chemotherapy-Combined Treatments

Marciniak,

Kciuk,

Mujwar

et al. 2023

Cancers

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“…For instance, knockout of the DUSP2 gene in mice led to the enhanced differentiation of TH17 cells and elevated secretion levels of pro-inflammatory cytokines, thereby exacerbating inflammatory symptoms in animal models of enteritis [30]. In yeasts, YVH1 serves as a conserved dual-specificity phosphatase involved in the growth, differentiation, and virulence of fungal pathogens affecting plants and animals [31,32]. Although the DSP domain contributes to human MAPK signaling regulation, for most cellular functions exerted by YVH1 in fungi, it primarily relies on the ZB domain [33].…”

Section: Introductionmentioning

confidence: 99%

Revealing the Complete Bispecific Phosphatase Genes (DUSPs) across the Genome and Investigating the Expression Patterns of GH_A11G3500 Resistance against Verticillium wilt

Deng,

Zhao

et al. 2024

IJMS

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DUSPs, a diverse group of protein phosphatases, play a pivotal role in orchestrating cellular growth and development through intricate signaling pathways. Notably, they actively participate in the MAPK pathway, which governs crucial aspects of plant physiology, including growth regulation, disease resistance, pest resistance, and stress response. DUSP is a key enzyme, and it is the enzyme that limits the rate of cell metabolism. At present, complete understanding of the DUSP gene family in cotton and its specific roles in resistance to Verticillium Wilt (VW) remains elusive. To address this knowledge gap, we conducted a comprehensive identification and analysis of four key cotton species: G. arboreum, G. barbadense, G. hirsutum, and G. raimondii. The results revealed the identification of a total of 120 DUSP genes in the four cotton varieties, which were categorized into six subgroups and randomly distributed at both ends of 26 chromosomes, predominantly localized within the nucleus. Our analysis demonstrated that closely related DUSP genes exhibited similarities in terms of the conserved motif composition and gene structure. A promoter analysis performed on the GhDUSP gene promoter revealed the presence of several cis-acting elements, which are associated with abiotic and biotic stress responses, as well as hormone signaling. A tissue expression pattern analysis demonstrated significant variations in GhDUSP gene expression under different stress conditions, with roots exhibiting the highest levels, followed by stems and leaves. In terms of tissue-specific detection, petals, leaves, stems, stamens, and receptacles exhibited higher expression levels of the GhDUSP gene. The gene expression analysis results for GhDUSPs under stress suggest that DUSP genes may have a crucial role in the cotton response to stress in cotton. Through Virus-Induced Gene Silencing (VIGS) experiments, the silencing of the target gene significantly reduced the resistance efficiency of disease-resistant varieties against Verticillium Wilt (VW). Consequently, we conclude that GH_A11G3500-mediated bispecific phosphorylated genes may serve as key regulators in the resistance of G. hirsutum to Verticillium Wilt (VW). This study presents a comprehensive structure designed to provide an in-depth understanding of the potential biological functions of cotton, providing a strong foundation for further research into molecular breeding and resistance to plant pathogens.

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Virtual Screening and Biochemical Evaluation to Identify the Allosteric Inhibitors of Dual Specificity Phosphatase 1

Park

Kim

Park

et al. 2019

Bulletin Korean Chem Soc

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Although a wealth of persuasive evidence was provided for the involvement of dual specificity phosphatase 1 (DUSP1) in cancers, depression, and hepatitis C virus replication, small-molecule inhibitors have been reported rarely. Because most competitive phosphatase inhibitors are disadvantageous in terms of pharmacological properties due to the possession of highly polar groups, we aim in this work to identify the allosteric DUSP1 inhibitors through the structure-based virtual screening. Using the modified proteinligand binding energy function involving an accurate molecular dehydration term, we identify six allosteric DUSP1 inhibitors that impair the enzymatic activity at low-micromolar level. Consistent with the kinetic analysis on the inhibitory mechanism, docking simulation results indicate that the newly discovered inhibitors would bind in the peripheral binding pocket of DUSP1 in preference to the active site. Besides the micromolar-level biochemical potency, the allosteric DUSP1 inhibitors found in this work may be meritorious over the competitive ones because of the lack of the reactive moiety to mimic the substrate phosphate group. Hence, they are anticipated to serve as a good starting point for the development of new therapeutics against cancers and neurological diseases.

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Two intermediate states of the conformational switch in dual specificity phosphatase 13a

Cited by 3 publications

References 35 publications

In Vitro and In Silico Investigation of BCI Anticancer Properties and Its Potential for Chemotherapy-Combined Treatments

In Vitro and In Silico Investigation of BCI Anticancer Properties and Its Potential for Chemotherapy-Combined Treatments

Revealing the Complete Bispecific Phosphatase Genes (DUSPs) across the Genome and Investigating the Expression Patterns of GH_A11G3500 Resistance against Verticillium wilt

Virtual Screening and Biochemical Evaluation to Identify the Allosteric Inhibitors of Dual Specificity Phosphatase 1

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