Question

How does temperature and pH (physically) denature enzymes?

Answer 1

I understand that it changes the shape of the active site, but how?

Answer 2

I'm sure @blues can give a better explanation (and/or correct me if I'm wrong), but it's my understanding that a change in temperature/pH will affect some of the bonds that hold the protein together in its folded state. If the pH gets more acidic, for example, that means more amino acid side chains will be protonated, changing their charges and thus changing how they interact with other amino acids.

Answer 3

Calliope has covered the nuts and bolts of it.

The amino acids in a protein are all bonded with peptide bonds, which are covalent. The actual structure the peptide chain folds into is held together by much weaker non-covalent interactions between parts of the chain which end up being close together in space. There are some covalent bonds called disulfide bridges between cysteine residues, but for the most part non-covalent.

A lot of these non bonds are weak electrostatic interactions. Putting more energy into the system by heating the protein increases the frequency with which they are broken. Changing the pH of the system messes with their electric properties. So different reasons, same effect: destablised bonds and, with enough input of energy, destablised protein.