Negative cooperativity associated with binding of multivalent carbohydrates to lectins. Thermodynamic analysis of the "multivalency effect"

Tarun K. Dam, René Roy, Daniel Pagé, Curtis F. Brewer

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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/G1c-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-Ο-(α-D-mannopyranosyl)-α-D-mannopyranoside residues to ConA and DGL were subjected to Hill plot analysis. Hill plots of the binding of monovalent methyl 3,6-di-Ο-(α-D-mannopyranosyl)-α-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.

Original languageEnglish (US)
Pages (from-to)1351-1358
Number of pages8
JournalBiochemistry
Volume41
Issue number4
DOIs
StatePublished - Jan 29 2002

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Thermodynamics
Lectins
Carbohydrates
Concanavalin A
Mannose
Titration
Biochemistry
Molecules
Entropy
Epitopes
Dioclea grandiflora lectin
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Negative cooperativity associated with binding of multivalent carbohydrates to lectins. Thermodynamic analysis of the "multivalency effect". / Dam, Tarun K.; Roy, René; Pagé, Daniel; Brewer, Curtis F.

In: Biochemistry, Vol. 41, No. 4, 29.01.2002, p. 1351-1358.

Research output: Contribution to journalArticle

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