  Recent experiments have revealed that the diffusivity of exothermic and fast
enzymes is enhanced when they are catalytically active, and different physical
mechanisms have been explored and quantified to account for this observation.
We perform measurements on the endothermic and relatively slow enzyme aldolase,
which also shows substrate-induced enhanced diffusion. We propose a new
physical paradigm, which reveals that the diffusion coefficient of a model
enzyme hydrodynamically coupled to its environment increases significantly when
undergoing changes in conformational fluctuations in a substrate-dependent
manner, and is independent of the overall turnover rate of the underlying
enzymatic reaction. Our results show that substrate-induced enhanced diffusion
of enzyme molecules can be explained within an equilibrium picture, and that
the exothermicity of the catalyzed reaction is not a necessary condition for
the observation of this phenomenon.
