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Cryo-EM structure and regulation of human NAD kinase.
Sci Adv
January 2025
Atelier de Biologie Chimie Informatique Structurale, Centre de Biologie Structurale, Univ Montpellier, CNRS, INSERM, 29 rue de Navacelles, 34090 Montpellier, France.
Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is a crucial reducing cofactor for reductive biosynthesis and protection from oxidative stress. To fulfill their heightened anabolic and reductive power demands, cancer cells must boost their NADPH production. Progrowth and mitogenic protein kinases promote the activity of cytosolic NAD kinase (NADK), which produces NADP, a limiting NADPH precursor.
View Article and Find Full Text PDFFluorescence Lifetime Imaging of NAD(P)H in Patients' Lymphocytes: Evaluation of Efficacy of Immunotherapy.
Cells
January 2025
Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 10/1 Minin and Pozharsky Sq., 603005 Nizhny Novgorod, Russia.
Background: The wide variability in clinical responses to anti-tumor immunotherapy drives the search for personalized strategies. One of the promising approaches is drug screening using patient-derived models composed of tumor and immune cells. In this regard, the selection of an appropriate in vitro model and the choice of cellular response assay are critical for reliable predictions.
View Article and Find Full Text PDFStructure, kinetics, and mechanism of Pseudomonas putida sulfoquinovose dehydrogenase, the first enzyme in the sulfoglycolytic Entner-Doudoroff pathway.
Biochem J
January 2025
School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
The sulfosugar sulfoquinovose (SQ) is catabolized through the sulfoglycolytic Entner-Doudoroff pathway, beginning with the oxidation of SQ to sulfogluconolactone by SQ dehydrogenase. We present a comprehensive structural and kinetic characterization of Pseudomonas putida SQ dehydrogenase (PpSQDH). PpSQDH is a tetrameric enzyme belonging to the short-chain dehydrogenase/reductase (SDR) superfamily with a strong preference for NAD+ over NADP+.
View Article and Find Full Text PDFStructure-guided insights into TIR-mediated bacterial and eukaryotic immunity.
Structure
January 2025
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. Electronic address:
Within the course of evolution, TIR (Toll/interleukin-1 receptor) domains acquired a myriad of functional specificities. This has significantly added to their well-established roles in innate immune signaling. These additional functions include nicotinamide adenine dinucleotide (NAD)(P) hydrolase, RNA/DNA nuclease (in plants), CN (cyclic nucleotide) cyclase, and base exchanger activities.
View Article and Find Full Text PDFAging is characterized by extensive metabolic dysregulation. Redox coenzyme nicotinamide adenine dinucleotide (NAD) can exist in oxidized (NAD) or reduced (NADH) states, which together form a key NADH/NAD redox pair. Total levels of NAD decline with age in a tissue-specific manner, thereby playing a significant role in the aging process.
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