Growing evidence supports the view that enzymatic activity results from a subtle interplay between chemical kinetics and molecular motions. A systematic analysis is performed here to delineate the type and level of coupling between catalysis and conformational mechanics. The dynamics of a set of 98 enzymes representative of different EC classes are analyzed with the Gaussian network model (GNM) and compared with experimental data. In more than 70% of the examined enzymes, the global hinge centers predicted by the GNM are found to be colocalized with the catalytic sites experimentally identified. Low translational mobility (< 7%) is observed for the catalytic residues, consistent with the fine-tuned design of enzymes to achieve precise mechanochemical activities. Ligand binding sites, while closely neighboring catalytic sites, enjoy a moderate flexibility to accommodate the ligand binding. These findings could serve as additional criteria for assessing drug binding residues and could lessen the computational burden of substrate docking searches.