Fig. 1: Strategy for designing allosteric sites in protein complexes.
a, Strategy for the design of an allosteric site in a protein dimer complex. The non-catalytic subunit (pink) has a pseudo-active site, the function of which (for example, the ability to bind to a small molecule) has been lost during evolution. By computationally restoring the lost function, this pseudo-active site is engineered to be an allosteric site that controls a function of the active site in the catalytic subunit (cyan) upon the small (that is, effector) molecule binding. b, Overview of design of allosteric sites in E. hirae V1-ATPase. The active sites in the catalytic interface and the pseudo-active sites in the non-catalytic interfaces are indicated by solid and dashed arrows, respectively, in the hexameric ring of V1 consisting of A subunits (cyan) and B subunits (pink). The rotor of the D and F subunits (grey) is located in the centre of the ring. The pseudo-active sites in the non-catalytic interfaces are designed to be ATP-binding allosteric sites that control the ATP hydrolysis function of the active sites in the catalytic interfaces.
