%0 Journal Article
%T Cation-responsive cavity expansion of valinomycin revealed by cryogenic ion trap infrared spectroscopy.
%A Hirata K
%A Sato E
%A Lisy JM
%A Ishiuchi SI
%A Fujii M
%J Phys Chem Chem Phys
%V 25
%N 2
%D Jan 2023 4
%M 36519454
%F 3.945
%R 10.1039/d2cp04570b
%X Valinomycin (VM) is a natural K+-selective ionophore that transports K+ through the cell membrane. VM captures K+ in its central cavity with a C3-symmetric β-turn-like backbone. Although the binding affinity is drastically decreased for the VM-sodium (Na+VM) complex with respect to K+VM, VM holds relatively high affinity to Rb+ and Cs+. The high affinity for larger ions irrespective of ionic size seems to conflict with the expected optimal size matching model and raises questions on what factors determine ion selectivity. A combination of infrared spectroscopy with supporting computational calculations reveals that VM can accommodate larger Rb+ and Cs+ by flexibly changing its cavity size with the elongation of its folded β-turn-like backbone. The high affinity to Rb+ and Cs+ can be ascribed to a size-dependent cavity expansion. These findings provide a new perspective on molecular recognition and selectivity beyond the conventional size matching model.