HYDROGEN-BONDING PATTERN OF METHYL BETA-LACTOSIDE BINDING TO THE RICINUS-COMMUNIS LECTINS

The binding of O-methyl and fluorodeoxy derivatives of methyl beta-lac toside to the Ricinus communis toxin (RCA60) and agglutinin (RCA120) w as studied in order to determine the donor/acceptor relationships of t he hydrogen bonds between the hydroxyl groups of methyl beta-lactoside and the binding sites of the lectins. Free energy contributions of th e hydrogen bonds at each position have been estimated from these data and from those previously reported for the monodeoxy derivatives [Rive ra-Sagredo, A., Solis, D., Diaz-Maurino, T., Jimenez-Barbero, J. & Mar tin-Lomas, M. (1991) Eur J. Biochem. 197,217-228; Rivera-Sagredo, A., Jimenez-Barbero, J., Martin-Lomas, M., Solis, D. & Diaz-Maurino, T. (1 992) Carbohydr Res. 232, 207-226]. The nature of the groups of the lec tins involved in hydrogen bonding has been predicted on the basis of t he free energy data. Analysis of the results indicates that both the C -3' and C-4' hydroxyl groups act as hydrogen-bond donors to charged gr oups of both RCA60 and RCA120. The C-6' and probably also the C-2' hyd roxyl groups participate both as donors and as acceptors of two hydrog en bonds with neutral groups of the lectins. And finally, the C-6 hydr oxyl group possibly acts as a donor of a weak hydrogen bond to a neutr al group in RCA60, but not in RCA120. The results provide a molecular basis to explain some features of the binding specificity of the lecti ns. Comparison of RCA60 binding data with the recently refined X-ray c rystal structure of the RCA60-lactose complex shows similarities but a lso some discrepancies that can be attributed to the marked influence of the pH on the carbohydrate-lectin interaction.