The plant apoplast during plant-pathogen interactions is an ancient battleground that holds an intriguing range of attacking enzymes and counteracting inhibitors. Examples are pathogen xylanases and polygalacturonases that are inhibited by plant proteins like TAXI, XIP, and PGIP; and plant glucanases and proteases, which are targeted by pathogen proteins such as GIP1, EPI1, EPIC2B, and AVR2. These seven well-characterized inhibitors have different modes of action and many probably evolved from inactive enzymes themselves. Detailed studies of the structures, sequence variation, and mutated proteins uncovered molecular struggles between these enzymes and their inhibitors, resulting in positive selection for variant residues at the contact surface, where single residues determine the outcome of the interaction.
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http://dx.doi.org/10.1016/j.pbi.2008.04.007 | DOI Listing |
Clin Transl Sci
February 2025
Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, University of Florida College of Pharmacy, Gainesville, Florida, USA.
Tramadol, the 41st most prescribed drug in the United States in 2021 is a prodrug activated by CYP2D6, which is highly polymorphic. Previous studies showed enzyme-inhibitor affinity varied between different CYP2D6 allelic variants with dextromethorphan and atomoxetine metabolism. However, no study has compared tramadol metabolism in different CYP2D6 alleles with different CYP2D6 inhibitors.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Department of Immunology, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, China. Electronic address:
Objective: Aberrant 6-phosphofructo-2kinase/fructose-2,6-bisphoshatase 3 (PFKFB3) expression is tightly correlated with multiple steps of tumorigenesis; however, the pathological significance of PFKFB3 in macrophages in patients with rheumatoid arthritis (RA) remains obscure. In this study, we examined whether PFKFB3 modulates macrophage activation and promotes RA development.
Method: Peripheral blood mononuclear cells (PBMCs) from patients with RA, THP-1 cells, and bone marrow-derived macrophages from conditional PFKFB3-knockout mice were used to investigate the mechanism underlying PFKFB3-induced macrophage regulation of RA.
J Chem Ecol
January 2025
Department of Nematology, University of California Riverside, Riverside, CA, USA.
Plants produce defensive toxins to deter herbivores. In response, some specialized herbivores evolved resistance and even the capacity to sequester toxins, affecting interactions at higher trophic levels. Here, we test the hypothesis that potential natural enemies of specialized herbivores are differentially affected by plant toxins depending on their level of adaptation to the plant-herbivore system.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Beijing Key Laboratory for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing 100083, China.
The flexibility and programmability of CRISPR-Cas technology have made it one of the most popular tools for biomarker diagnostics and gene regulation. Especially, the CRISPR-Cas12 system has shown exceptional clinical diagnosis and gene editing capabilities. Here, we discovered that although the top loop of the 5' handle of guide RNA can undergo central splitting, deactivating CRISPR-Cas12a, the segments can dramatically restore CRISPR function through nucleic acid self-assembly or interactions with small molecules and aptamers.
View Article and Find Full Text PDFJ Clin Exp Hepatol
December 2024
Biochemistry and Molecular Biology Department, Theodor Bilharz Research Institute, Giza, Egypt.
Background: Liver fibrosis is a serious global health issue, but current treatment options are limited due to a lack of approved therapies capable of preventing or reversing established fibrosis.
Aim: This study investigated the antifibrotic effects of a synthetic peptide derived from α-lactalbumin in a mouse model of thioacetamide (TAA)-induced liver fibrosis.
Methods: analyses were conducted to assess the physicochemical properties, pharmacophore features, and docking interactions of the peptide.
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