Why does an enzyme not work as well if its active site is changed?

Enzymes are generally very carefully formed in order to catalyze a specific reaction for a specific molecule. The active site is folded in such as way to just allow the desired substrate to fit into it (like a puzzle piece), so changing the site will make it more difficult for this binding to occur. If the binding is more difficult the reaction will be inhibited, hence the enzyme won't work as well (if at all).