Thermodynamics of Multivalent Carbohydrate−Lectin Cross-Linking Interactions: Importance of Entropy in the Bind and Jump Mechanism
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- 作者：Tarun K. Dam ; Thomas A. Gerken ; C. Fred Brewer
- 刊名：Biochemistry
- 出版年：2009
- 出版时间：May 12, 2009
- 年：2009
- 卷：48
- 期：18
- 页码：3822-3827
- 全文大小：845K
- 年卷期：v.48,no.18(May 12, 2009)
- ISSN：1520-4995
文摘
The high affinity (Kd = 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 106 Da and 2300 GalNAcα1-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 GalNAcα1-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.