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Directed evolution of diacylglycerol acyltransferases 2 promotes lipids and triglyceride accumulation.
Plant Mol Biol
January 2025
College of Life Sciences, Northwest A & F University, Xi'an, 710000, China.
Triacylglycerol (TAG) is a major component of plant-neutral lipids. Diacylglycerol acyltransferase 2 (DGAT2) plays an important role in plant oil accumulation by catalyzing the final step of the Kennedy pathway. In this study, ten DGAT2 sequences were originating from different oil crops into the TAG-deficient yeast strain H1246, to compare their enzyme activity of oil synthesis and filter out potential amino acid residue sites for directed evolution.
View Article and Find Full Text PDFSRF and CBP jointly regulate integrin β6 overexpression in head and neck squamous cell carcinomas.
Cell Signal
January 2025
Department of Basic Medical Science & Department of Stomatology, School of Medicine, Xiamen University, Xiamen, Fujian, China. Electronic address:
Overexpression of integrin β6 (ITGB6) is crucially linked to the invasion and metastasis of head and neck squamous cell carcinoma (HNSCC). The molecular mechanisms driving ITGB6 upregulation in HNSCC are not well understood. Our study comprehensively analyzed the transcriptional regulation and epigenetic modification mechanisms affecting ITGB6 transcription.
View Article and Find Full Text PDFMolecular modelling and optimization of a high-affinity nanobody targeting the nipah virus fusion protein through in silico site-directed mutagenesis.
Comput Biol Chem
January 2025
Virology and Vaccine Research and Development Program, Department of Science and Technology-Industrial Technology Development Institute, Taguig City, Metro Manila 1631, Philippines; S&T Fellows Program, Department of Science and Technology, Taguig City, Metro Manila 1631, Philippines; Department of Biology, College of Arts and Sciences, University of the Philippines - Manila, Metro Manila 1000, Philippines. Electronic address:
Nipah virus (NiV) is a re-emerging zoonotic pathogen with a high mortality rate and no effective treatments, prompting the search for new antiviral strategies. While conventional antiviral drugs are often limited by issues such as poor specificity, off-target effects, and resistance development, nanobodies offer distinct advantages. These small, single-domain antibodies exhibit high specificity and stability, making them ideal candidates for antiviral therapy.
View Article and Find Full Text PDFChemical Logic of Peptide Branching by Iterative Nonlinear Nonribosomal Peptide Synthetases.
Biochemistry
January 2025
Department of Chemistry, Washington University in St. Louis, One Brookings Drive, St. Louis, Missouri 63130, United States.
Branch-point syntheses in nonribosomal peptide assembly are rare but useful strategies to generate tripodal peptides with advantageous hexadentate iron-chelating capabilities, as seen in siderophores. However, the chemical logic underlying the peptide branching by nonribosomal peptide synthetase (NRPS) often remains complex and elusive. Here, we review the common strategies for the biosynthesis of branched nonribosomal peptides (NRPs) and present our biochemical investigation on the NRPS-catalyzed assembly of fimsbactin A, a branched mixed-ligand siderophore produced by the human pathogenic strain .
View Article and Find Full Text PDFDesign of ()-3-(5-Thienyl)carboxamido-2-aminopropanoic Acid Derivatives as Novel NMDA Receptor Glycine Site Agonists: Variation in Molecular Geometry to Improve Potency and Augment GluN2 Subunit-Specific Activity.
J Med Chem
January 2025
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DK-2100, Denmark.
NMDA receptor ligands have therapeutic potential in neurological and psychiatric disorders. We designed ()-3-(5-thienyl)carboxamido-2-aminopropanoic acid derivatives with nanomolar agonist potencies at NMDA receptor subtypes (GluN12/A-D). These compounds are superagonists at GluN1/2C compared to glycine and partial to full agonists at GluN1/2A and GluN1/2D but display functional antagonism at GluN1/2B due to low agonist efficacy.
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