Seminar

Breaking the limits in understanding glycan recognition by NMR

Prof. Jesús Jimenez Barbero

Molecular recognition by specific targets is at the heart of the life processes. The interactions between proteins (lectins, enzymes, antibodies) and carbohydrates mediate a broad range of biological activities, from fertilization and tissue maturation, to pathological processes. The elucidation of the mechanisms that govern how sugars are accommodated in the binding sites is a topic of interest. Given the inherent flexibility of sugars, we use NMR as key tool for deducing at atomic resolution molecular recognition processes in which glycans are involved, also assisted by a variety of biophysical techniques. I herein present the application of state-of-the-art NMR methods, both from the ligand and receptor’s perspective, to study molecular recognition processes between lectins of biomedical interest and glycans, especially focusing on human C-type lectins (DC-SIGN), galectins and siglecs. The fine details of the interaction for each type of lectin will be described, paying attention to the relative importance of polar (hydrogen bonding, electrostatic, cation-mediated) and non-polar (van der Waals, CH-π) forces in the recognition event, with especial emphasis on the application of novel NMR methods and on the analysis of the kinetics and thermodynamics of the binding event.[1-9] 1. A. Gimeno, et al. ACS Chem Biol. 2017, 12, 1104. 2. A. Canales, et al., Angew Chem Int Ed. 2017, 56, 14987. 3. B. Fernández de Toro, et al., Angew Chem Int Ed. 2018, 57, 15051. 4. A. Ardá & J. Jiménez-Barbero, Chem Commun. 2018, 54, 4761. 5. M. Delbianco et al., J Am Chem Soc. 2018, 140, 5421. 6. P. Valverde et al., ACS Chem Biol. 2019, 14, 1660. 7. A. Gimeno et al., Angew Chem Int Ed Engl. 2019, 58, 7268. 8. L. Lebedel et al., Angew Chem Int Ed Engl. 2019, 58, 13758. 9. L. Unione et al., ACS Central Sci. 2019, 5, 1554 10. A. Gimeno et al., Curr Opin Struct Biol. 2020, 62, 22