This study offers a detailed mechanistic investigation of hostguest encapsulation behavior in a new enzyme-mimetic metal-ligand host and provides the first observation of a conformational selection mechanism (as opposed to induced fit) in a supramolecular system. The Ga4L4 host described features a C-3-symmetric ligand motif with meta-substituted phenyl spacers, which enables the host to initially self-assemble into an S-4-symmetric structure and then subsequently isomerize to a T-symmetric tetrahedron for better accommodation of a sufficiently large guest. Selective inversion recovery H-1 NMR studies provide structural insights into the self-exchange behaviors of the host and the guest individually in this dynamic system. Kinetic analysis of the encapsulation-isomerization event revealed that increasing the concentration of guest inhibits the rate of host-guest relaxation, a key distinguishing feature of conformational selection. A comprehensive study of this simple enzyme mimic provides insight into analogous behavior in biophysics and enzymology and aims to inform the design of efficient self-assembled microenvironment catalysts.