2011
DOI: 10.1016/j.jmb.2010.11.058
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Tracing the Detail: How Mutations Affect Binding Modes and Thermodynamic Signatures of Closely Related Aldose Reductase Inhibitors

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Cited by 24 publications
(34 citation statements)
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“…2c) also demonstrated apparent entropy-enthalpy compensation, attributed by the authors to solvent ordering effects [8]. Recent work has also found that receptor mutations can cause minimal changes in the overall free energy of binding and minimal structural changes in X-ray or NMR structures of bound ligands but extreme changes in the enthalpic and entropic contributions to binding, interpreted as suggesting large changes in the mechanism of binding [1,2,6]. …”
Section: Experimental Evidence For Compensationmentioning
confidence: 99%
See 1 more Smart Citation
“…2c) also demonstrated apparent entropy-enthalpy compensation, attributed by the authors to solvent ordering effects [8]. Recent work has also found that receptor mutations can cause minimal changes in the overall free energy of binding and minimal structural changes in X-ray or NMR structures of bound ligands but extreme changes in the enthalpic and entropic contributions to binding, interpreted as suggesting large changes in the mechanism of binding [1,2,6]. …”
Section: Experimental Evidence For Compensationmentioning
confidence: 99%
“…These methods must either use a crude model of of ligand entropy with poor accuracy and convergence properties [9193] or ignore differences in ligand binding entropies altogether and assume enthalpies alone are predictive of affinity, a point contested by both experimental [6,7] and computational [74] studies (also recently reviewed [84]).…”
Section: Ramifications For Ligand Engineeringmentioning
confidence: 99%
“…In the crystal structure of T113S/IDD383 complex, the percentages of the two corresponding configurations are 72% and 28%; and in the T113S/IDD594 complex, they are 68% and 32% (31). …”
mentioning
confidence: 99%
“…Thus, both MS gas‐phase measurements and IC 50 solution studies indicate that FID is the strongest binder. This is even more the case in the published11, 12 isothermal titration calorimetry (ITC) studies, for which the ratio between the K d of 594 and of FID is 10.…”
Section: Resultsmentioning
confidence: 96%
“…On the other hand, some of them also have another moiety, which binds to the so‐called “specificity pocket,” formed by residues of the three external loops of AR adjacent to the anion binding pocket 10. In solution, FID binds AR more strongly (with the hydantoin moiety; K d : 6.5 n M 11) than 594 (with the carboxylic acid moiety; K d : 61 n M 12), as confirmed in the present study by competition experiments monitored by native MS and by IC 50 measurements. To characterize the binding in solution, we have also measured the IC 50 values (a measure of binding in the case of an enzyme).…”
Section: Introductionmentioning
confidence: 99%