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Residual Ligand Entropy in the Binding of p -Substituted Benzenesulfonamide Ligands to Bovine Carbonic Anhydrase II

Sto?ckmann, H, Bronowska, A, Syme, NR, Thompson, GS, Kalverda, AP, Warriner, SL, Homans, SW (2008) Residual Ligand Entropy in the Binding of p -Substituted Benzenesulfonamide Ligands to Bovine Carbonic Anhydrase II. Journal of the American Chemical Society, 130 . pp. 12420-12426. ISSN 0002-7863. (doi:10.1021/ja803755m) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1021/ja803755m

Abstract

In studies on the thermodynamics of ligand-protein interactions, it is often assumed that the configurational and conformational entropy of the ligand is zero in the bound state (i.e., the ligand is rigidly fixed in the binding pocket). However, there is little direct experimental evidence for this assumption, and in the case of binding of p-substituted benzenesulfonamide inhibitors to bovine carbonic anhydrase II (BCA II), the observed thermodynamic binding signature derived from isothermal titration calorimetry experiments leads indirectly to the conclusion that a considerable degree of residual entropy remains in the bound ligand. Specifically, the entropy of binding increases with glycine chain length n, and strong evidence exists that this thermodynamic signature is not driven by solvent reorganization. By use of heteronuclear (15)N NMR relaxation measurements in a series (n = 1-6) of (15)N-glycine-enriched ligands, we find that the observed thermodynamic binding signature cannot be explained by residual ligand dynamics in the bound state, but rather results from the indirect influence of ligand chain length on protein dynamics.

Item Type: Article
DOI/Identification number: 10.1021/ja803755m
Subjects: Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: G. Thompson
Date Deposited: 23 Jan 2019 20:30 UTC
Last Modified: 30 May 2019 08:47 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/71815 (The current URI for this page, for reference purposes)
Thompson, GS: https://orcid.org/0000-0001-9399-7636
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