Secondary Binding Interactions in a Synthetic Receptor for Trimethyllysine.
We have systematically studied how secondary interactions with neighboring lysine (Lys) and arginine (Arg) residues influence the binding and selectivity of the synthetic receptor A2 N for trimethyllysine (Kme3 ). Multiple secondary binding sites on A2 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 KmeX (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 A2 N to KmeX 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.
Department of Chemistry, CB 3290, University of North Carolina, Chapel Hill, NC 27599 (USA).
Nicholas K
NK
Pinkin
Department of Chemistry, CB 3290, University of North Carolina, Chapel Hill, NC 27599 (USA).
Ina
I
Liu
Department of Chemistry, CB 3290, University of North Carolina, Chapel Hill, NC 27599 (USA).
Jessicca D
JD
Abron
Department of Chemistry, CB 3290, University of North Carolina, Chapel Hill, NC 27599 (USA). mlwaters@unc.edu.
Marcey L
ML
Waters
D001120:Arginine / Q000737:chemistry*; D001665:Binding Sites; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry*; D011485:Protein Binding; D062165:Receptors, Artificial / Q000138:chemical synthesis* / Q000737:chemistry; D013816:Thermodynamics
D062165:Receptors, Artificial; C003712:trimethyllysine; D001120:Arginine; D008239:Lysine
molecular recognition in water; post-translational modifications; salt bridges; synthetic receptors; trimethyllysine recognition