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Secondary Binding Interactions in a Synthetic Receptor for Trimethyllysine
Author(s) -
Pinkin Nicholas K.,
Liu Ina,
Abron Jessicca D.,
Waters Marcey L.
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201502302
Subject(s) - chemistry , computational biology , biophysics , microbiology and biotechnology , biology
We have systematically studied how secondary interactions with neighboring lysine (Lys) and arginine (Arg) residues influence the binding and selectivity of the synthetic receptor A 2 N for trimethyllysine (Kme 3 ). Multiple secondary binding sites on A 2 N are formed by carboxylates rigidly positioned over aromatic rings, a motif that has been shown to stabilize salt bridges. We varied the spacing between Kme X ( X =0, 3) and an ancillary Lys or Arg and measured binding by isothermal titration calorimetry (ITC). These studies revealed that both neighboring residues improve the binding of A 2 N to Kme X by approximately 1 kcal mol −1 , with little influence of the spacing. Nonetheless, the improvement in affinity caused by Arg is enthalpically driven, while for Lys it is entropically driven, suggesting different mechanisms by which the residues interact with the secondary binding site.