title: Negative cooperativity associated with binding of multivalent carbohydrates to lectins. Thermodynamic analysis of the "multivalency effect".
abstract: Our previous study demonstrated that isothermal titration microcalorimetry (ITC) could be used to determine the thermodynamics of binding of a series of synthetic multivalent carbohydrates to the Man/Glc-specific lectins concanavalin A (ConA) and Dioclea grandiflora lectin (DGL) [Dam, T. K., Roy, R., Das, S. K., Oscarson, S. and Brewer, C. F. (2000) J. Biol. Chem. 275, 14223-14230]. The higher affinities of the multivalent carbohydrates for the two lectins were shown to be due to their greater positive entropy of binding contributions relative to monovalent analogues. In the present study, ITC data from our previous report for binding of di-, tri-, and tetravalent carbohydrate analogues possessing terminal 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside residues to ConA and DGL were subjected to Hill plot analysis. Hill plots of the binding of monovalent methyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside to ConA and DGL are linear with slopes near 1.0, demonstrating a lack of binding cooperativity and allosteric transitions in the proteins. However, Hill plots for the binding of the di-, tri-, and tetravalent trimannoside analogues to both lectins are curvilinear with decreasing tangent slopes below 1.0, indicating increasing negative cooperativity upon binding of the analogues to the lectins. The curvilinear Hill plots are consistent with decreasing affinity and functional valencies of the multivalent analogues upon sequential binding of lectin molecules to the carbohydrate epitopes of the analogues. The following paper [Dam, T. K., Roy, R., Pagé, D., and Brewer, C. F. (2002) Biochemistry 41, 1359-1363] provides direct evidence of the decreasing affinity constants of multivalent carbohydrates upon sequential binding of lectin molecules.
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Tarun K
authors.initials: TK
authors.lastname: Dam
authors.forename: René
authors.initials: R
authors.lastname: Roy
authors.forename: Daniel
authors.initials: D
authors.lastname: Pagé
authors.forename: C Fred
authors.initials: CF
authors.lastname: Brewer
mesh_terms: D002236:Carbohydrate Conformation; D050260:Carbohydrate Metabolism; D002240:Carbohydrate Sequence; D037102:Lectins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D013816:Thermodynamics
chemical_list: D037102:Lectins