The protein environment of enzyme active sites is important in facilitating enzymatic reactions. The protein binds the substrate holding it in a particular geometry so that nearby functional groups are oriented to stabilize the transition state. These functional groups are involved in the reaction mechanism acting as hydrogen-bond partners, providing an electrostatic environment favorable for the reaction, and taking part as acidic or basic groups in proton-transfer reactions. The reaction kinetics are controlled by these local interactions with the protein. This static picture of the protein/substrate interactions, however, is an incomplete description of the catalytic process because fluctuations of these protein functional groups can also be important in the reaction mechanism. In enzymatic hydrogen-transfer reactions, for example, fluctuations of the protein can cause a time-dependent variation in the donor-acceptor separation resulting in large changes in the hydrogen-transfer barrier height. We use 2D IR correlation spectroscopy to study the fluctuations of the enzyme active site and the specific interactions that control the chemistry.