Equilibrium binding ligands usually increase protein thermal stability by an amount proportional to the concentration and affinity of the ligand. High-throughput screening for the discovery of drug-like compounds uses an assay based on thermal stabilization. The mathematical description of this stabilization is well developed, and the method is widely applicable to the characterization of ligand-protein binding equilibrium. However, numerous cases have been experimentally observed where equilibrium binding ligands destabilize proteins, i.e., diminish protein melting temperature by an amount proportional to the concentration and affinity of the ligand. Here, we present a thermodynamic model that describes ligand binding to the native and unfolded (denatured) protein states explaining the combined stabilization and destabilization effects. The model also explains nonsaturation and saturation effects on the protein melting temperature when the ligand concentration significantly exceeds the protein concentration. Several examples of the applicability of the model are presented, including specific sulfonamide binding to recombinant hCAII, peptide and ANS binding to the Polo-box domain of Plk1, and zinc ion binding to the recombinant porcine growth hormone. The same ligands may stabilize and destabilize different proteins, and the same proteins may be stabilized and destabilized by different ligands.
The advanced glycoxidation end products (AGEs) and lipoxidation end products (ALEs) contribute to the development of diabetic complications and of other pathologies. The review discusses the possibilities of counteracting the formation and stimulating the degradation of these species by pharmaceuticals and natural compounds. The review discusses inhibitors of ALE and AGE formation, cross-link breakers, ALE/AGE elimination by enzymes and proteolytic systems, receptors for advanced glycation end products (RAGEs) and blockade of the ligand-RAGE axis.
Non-enzymatic protein modifications occur inevitably in all living systems. Products of such modifications accumulate during aging of cells and organisms and may contribute to their age-related functional deterioration. This review presents the formation of irreversible protein modifications such as carbonylation, nitration and chlorination, modifications by 4-hydroxynonenal, removal of modified proteins and accumulation of these protein modifications during aging of humans and model organisms, and their enhanced accumulation in age-related brain diseases.
Carotenoids are versatile isoprenoids that are important in food quality and health promotion. There is a need to establish recommended dietary intakes/nutritional reference values for carotenoids. Research on carotenoids in agro-food and health is being propelled by the two multidisciplinary international networks, the Ibero-American Network for the Study of Carotenoids as Functional Foods Ingredients (IBERCAROT; http://www.cyted.org ) and the European Network to Advance Carotenoid Research and Applications in Agro-Food and Health (EUROCAROTEN; http://www.eurocaroten.eu ). In this review, considerations for their safe and sustainable use in products mostly intended for health promotion are provided. Specifically, information about sources, intakes, and factors affecting bioavailability is summarized. Furthermore, their health-promoting actions and importance in public health in relation to the contribution of reducing the risk of diverse ailments are synthesized. Definitions and regulatory and safety information for carotenoid-containing products are provided. Lastly, recent trends in research in the context of sustainable healthy diets are summarized. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 12 is March 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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