Once the substrate is bound and oriented to the active site, catalysis can begin. The residues of the catalytic site are typically very close to the binding site, and some residues can have dual-roles in both binding and catalysis.
Catalytic residues of the site interact with the substrate to lower the activation energy of a reaction and thereby make it proceed faster. They do this by a number of different mechanisms including the approximation of the reactants, nucleophilic/electrophilic catalysis and acid/base catalysis. These mechanisms will be explained below.