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Molecular Research of Therapeutic Target Enzymes

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 20 April 2025 | Viewed by 879

Special Issue Editors


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Guest Editor
Department of Chemistry, Soongsil University Seoul 06978, Republic of Korea
Interests: structural biology; immune system signaling; cell death signaling

E-Mail
Guest Editor
Department of Chemistry, Soongsil University, Seoul 06978, Republic of Korea
Interests: structural biology; enzyme characterization; nitrogenase assembly
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Enzymes are biological catalysts that play essential roles in various physiological and pathological processes. Their involvement in the regulation of metabolic pathways, signal transduction, gene expression, and epigenetic modifications underscores their indispensability. The molecular-level research of therapeutic target enzymes holds the potential to revolutionize the landscape of modern medicine. These enzymes, capable of modulating the activity or function of substrates, cofactors, or inhibitors, offer avenues for precision therapies and targeted drug design.

In this Special Issue, we invite original research articles and reviews that delve into the broad spectrum of molecular-level research on therapeutic target enzymes. Topics of interest encompass their structure, function, mechanism, regulation, interaction, and evolution. We also welcome studies examining the potential applications of therapeutic target enzymes in the diagnosis, treatment, or prevention of various diseases, such as cancer, inflammation, infection, neurodegeneration, and metabolic disorders. The exploration of molecular-level research across multiple disciplines, including biochemistry, molecular biology, pharmacology, and medicinal chemistry, is highly encouraged. In addition, we actively seek submissions focusing on innovative technologies and methodologies employed in the molecular-level research of therapeutic target enzymes. This encompasses groundbreaking experimental approaches, advanced computational modeling, and high-throughput screening methods that augment our capacity to unravel the intricate molecular complexities of these critical biological entities. Our aspiration is that this Special Issue will offer a comprehensive and updated overview of the current state of the art and future directions in the dynamic field of molecular research of therapeutic target enzymes. We look forward to receiving your valuable contributions in advancing our understanding of these crucial components and their implications for the future of medical sciences.

Prof. Dr. Jinkuk Yang
Dr. Wonchull Kang
Guest Editors

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Keywords

  • enzyme kinetics
  • molecular biology
  • therapeutics
  • catalysis
  • drug design
  • precision medicine
  • therapeutic applications
  • biochemical regulation
  • enzyme evolution

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Published Papers (2 papers)

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16 pages, 8664 KiB  
Article
Visualizing the Cellular and Subcellular Distribution of Fms-like Tyrosine Kinase 3 (Flt3) and Other Neuronal Proteins Using Alkaline Phosphatase (AP) Immunolabeling
by Yuqin Yin, Kathleen Z. He, Jane Kirby, Ishraq A. Haque and Xin Tang
Int. J. Mol. Sci. 2025, 26(5), 2284; https://doi.org/10.3390/ijms26052284 - 4 Mar 2025
Abstract
Precisely localizing the spatial distribution of proteins within various brain cell types and subcellular compartments, such as the synapses, is essential for generating and testing hypotheses to elucidate their roles in brain function. While the fms-like tyrosine kinase-3 (Flt3) has been extensively studied [...] Read more.
Precisely localizing the spatial distribution of proteins within various brain cell types and subcellular compartments, such as the synapses, is essential for generating and testing hypotheses to elucidate their roles in brain function. While the fms-like tyrosine kinase-3 (Flt3) has been extensively studied in the context of blood cell development and leukemia pathogenesis, its role in the brain remains poorly understood. Previous efforts to address this issue were hindered by the low expression levels of Flt3 and the limited sensitivity of the standard immunolabeling method, which were insufficient to reliably detect Flt3 protein in brain tissue. In this study, we systematically characterized Flt3 protein localization during brain development using a highly sensitive immunolabeling method based on alkaline phosphatase (AP) polymer biochemistry. This approach revealed a previously unrecognized neuron-selective Flt3 expression pattern in both mouse and human cerebella, with a developmental increase in total protein levels accompanied by a shift from a cytosolic to a dendritic subcellular distribution. Combining AP-polymer-based immunohistochemistry (AP-IHC) for Flt3 with conventional immunostaining of cell type marker proteins revealed parvalbumin- and calbindin-positive Purkinje cells to be the main cell type expressing Flt3 in the cerebellum. To validate the versatility of the AP-IHC method for detecting low-abundance neuronal proteins, we demonstrated robust labeling of Kir2.1, a potassium channel protein, in brain tissue sections from mouse, pig, and human samples. We further applied the AP-IHC method to human stem cell-derived neurons, effectively visualizing the postsynaptic density scaffold protein PSD95 within synapses. To our knowledge, this is the first study to employ an AP-IHC method combined with other standard immunofluorescent staining to co-detect weakly expressed neuronal proteins and other cellular markers in brain tissue and cultured neurons. Additionally, our findings uncover a previously unrecognized neuron-specific pattern of Flt3 expression in the cerebellum, laying the foundation for future mechanistic studies on its role in normal brain development and neurological disorders. Full article
(This article belongs to the Special Issue Molecular Research of Therapeutic Target Enzymes)
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21 pages, 19869 KiB  
Article
Deferasirox Targets TAOK1 to Induce p53-Mediated Apoptosis in Esophageal Squamous Cell Carcinoma
by Boyang Li, Shihui Liu, Xiaowan Zhou, Dongpu Hou, Huajie Jia, Rude Tang, Yunqing Zhang and Mengqiu Song
Int. J. Mol. Sci. 2025, 26(4), 1524; https://doi.org/10.3390/ijms26041524 - 11 Feb 2025
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Abstract
Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with a poor prognosis and limited effective treatment options. This study investigates the therapeutic potential of Deferasirox (DFO), an iron chelator, in ESCC by targeting TAOK1, an STE20-type kinase implicated in cancer development. [...] Read more.
Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with a poor prognosis and limited effective treatment options. This study investigates the therapeutic potential of Deferasirox (DFO), an iron chelator, in ESCC by targeting TAOK1, an STE20-type kinase implicated in cancer development. We demonstrate that DFO significantly inhibits the proliferation and colony formation of ESCC cells in a dose- and time-dependent manner. Mechanistic investigations reveal that DFO binds directly to TAOK1 and reduces its kinase activity. Proteomics and phosphorylated proteomic sequencing analysis further reveal that TAOK1 knocking down dramatically increased p53-mediated apoptosis. Moreover, the inhibition of TAOK1 by DFO or lenti-virus infection induces apoptosis in ESCC cells, as evidenced by the increased expression of p53, p-p53 (S15), p-p53 (S46), Puma, Noxa, and Bax, and the decreased expression of Bcl-2. Furthermore, in vivo studies using patient-derived xenograft (PDX) mouse models show that DFO treatment significantly reduces tumor volume without observable toxicity. Histological and immunohistochemical analyses confirm the down-regulation of TAOK1 and Ki-67, and the up-regulation of p53 expression in DFO-treated tumors. Our findings suggest that DFO exerts its antitumor effects in ESCC by targeting TAOK1, providing a potential therapeutic strategy for ESCC patients. Full article
(This article belongs to the Special Issue Molecular Research of Therapeutic Target Enzymes)
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