title: Thermodynamics of multivalent carbohydrate-lectin cross-linking interactions: importance of entropy in the bind and jump mechanism.
abstract: The high affinity (K(d) = 0.2 nM) of the soybean agglutinin (SBA), a tetrameric GalNAc specific lectin, for a modified form of porcine submaxillary mucin, a linear glycoprotein, with a molecular mass of approximately 10(6) Da and approximately 2300 GalNAcalpha1-O-Ser/Thr residues (Tn-PSM) has been ascribed to an internal diffusion mechanism that involves binding and jumping of the lectin from GalNAc to GalNAc residue of the mucin [Dam, T. K., et al. (2007) J. Biol. Chem. 282, 28256-28263]. Hill plot analysis of the raw ITC data shows increasing negative cooperativity, which correlates with an increasing number of lectin-mucin cross-linking interactions and decreasing favorable binding entropies. However, the affinity of bound SBA for other Tn-PSM molecules during cross-linking is much higher than that of free SBA for GalNAcalpha1-O-Ser, a monovalent analogue. The high affinity of bound SBA for GalNAc residues on other Tn-PSM molecules appears to be due to the favorable entropy of binding associated with the internal diffusion mechanism. Furthermore, the increasing negative cooperativity of SBA binding to Tn-PSM correlates with a decreasing level of internal diffusion of the lectin on the mucin as cross-linking occurs. These findings indicate the importance of the internal diffusion mechanism in generating large, favorable entropies of binding that drive lectin-mucin cross-linking interactions. The results are important for understanding the energetics of lectin-mucin cross-linking interactions that are associated with biological signaling on the surface of cells and the role of the internal diffusion mechanism in ligand-biopolymer interactions in general.
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: Thomas A
authors.initials: TA
authors.lastname: Gerken
authors.forename: C Fred
authors.initials: CF
authors.lastname: Brewer
mesh_terms: D001665:Binding Sites; D002236:Carbohydrate Conformation; D002241:Carbohydrates / Q000737:chemistry*; D004058:Diffusion; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D002241:Carbohydrates; D037102:Lectins