How do mutations make non-functional enzymes?

Mutations are changes to the base sequence. The base sequence determines the amino acid sequence. A different base sequence therefore codes for a different amino acid sequence. Amino acids interact with each other by H-bonds, ionic bonds, and disulphide bridges. When the amino acid sequence changes, these interactions and bonds also change.

Proteins are shaped by interactions between their amino acids. When the interactions between amino acids change, the 3D shape of the protein changes (tertiary structure). Enzymes work by interacting with substrates via their 'active site'. A change in protein shape will change the shape of the active site. The substrate cannot bind to the new shape of the active site so no enzyme-substrate complexes are formed so the enzyme cannot function.