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The Active-Site [4Fe-4S] Cluster in the Isoprenoid Biosynthesis Enzyme IspH Adopts Unexpected Redox States during Ligand Binding and Catalysis.
J Am Chem Soc
February 2024
Department of Chemistry and Biochemistry, Auburn University, 179 Chemistry Building, Auburn, Alabama 36849, United States.
()-4-Hydroxy-3-methylbut-2-enyl diphosphate reductase, or IspH (formerly known as LytB), catalyzes the terminal step of the bacterial methylerythritol phosphate (MEP) pathway for isoprene synthesis. This step converts ()-4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP) into one of two possible isomeric products, either isopentenyl diphosphate (IPP) or dimethylallyl diphosphate (DMAPP). This reaction involves the removal of the C4 hydroxyl group of HMBPP and addition of two electrons.
View Article and Find Full Text PDFThree distinct mechanisms underlying human γδ T cell-mediated cytotoxicity against malignant pleural mesothelioma.
Front Immunol
April 2023
Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Article Synopsis
- - Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer with limited treatment options, prompting the need for innovative therapies like immune effector cell-based treatments.
- - Researchers expanded γδ T cells from blood samples of healthy donors and MPM patients, testing their effectiveness against MPM cells using various assays, which indicated a moderate cytotoxic response.
- - These γδ T cells demonstrated three distinct mechanisms of action against MPM cells—through natural killer (NK) receptors, T cell receptors (TCRs), and CD16—suggesting their potential as a novel therapeutic approach in treating MPM.
Two Distinct Mechanisms Underlying γδ T Cell-Mediated Regulation of Collagen Type I in Lung Fibroblasts.
Cells
September 2022
Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan.
Article Synopsis
- Idiopathic pulmonary fibrosis is a severe lung disease that leads to death, and while current treatments can slow it down, they aren't cures.
- This study found that human γδ T cells can significantly lower collagen type I levels in lung fibroblasts, which is important for fibrosis, but only when they are in direct contact with those cells.
- The research also discovered that these T cells can produce soluble factors that independently reduce collagen levels, and that their effectiveness is influenced by specific immune signals like interferon-γ and interleukin-18, suggesting a potential new therapy using γδ T cell transfer.
De novo assembly and analysis of Polygonatum cyrtonema Hua and identification of genes involved in polysaccharide and saponin biosynthesis.
BMC Genomics
March 2022
Agronomy College, Guizhou University, Huaxi, Guiyang, Guizhou, 550025, P. R. China.
Background: The investigation of molecular mechanisms involved in polysaccharides and saponin metabolism is critical for genetic engineering of Polygonatum cyrtonema Hua to raise major active ingredient content. Up to now, the transcript sequences are available for different tissues of P. cyrtonema, a wide range scanning about temporal transcript at different ages' rhizomes was still absent in P.
View Article and Find Full Text PDFA Photo-Crosslinkable Biotin Derivative of the Phosphoantigen (E)-4-Hydroxy-3-Methylbut-2-Enyl Diphosphate (HMBPP) Activates Vγ9Vδ2 T Cells and Binds to the HMBPP Site of BTN3A1.
Chemistry
September 2017
Institut für Organische Chemie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
Vγ9Vδ2 T cells play an important role in the cross talk of the innate and adaptive immune system. For their activation by phosphoantigens (PAgs), both cell surface receptors, the eponymous Vγ9Vδ2 T cell antigen receptors (Vγ9Vδ2 TCRs) on Vγ9Vδ2 T cells and butyrophilin 3A1 (BTN3A1) on the phosphoantigen-"presenting" cell, are mandatory. To find yet undetected but further contributing proteins, a biotinylated, photo-crosslinkable benzophenone probe BioBP-HMBPP (2) was synthesized from a known allyl alcohol in nine steps and overall 16 % yield.
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