Oxyanion hole

An oxyanion hole is a pocket in the active site of an enzyme that stabilizes transition state negative charge on a deprotonated oxygen or alkoxide.

[1] The pocket typically consists of backbone amides or positively charged residues.

Stabilising the transition state lowers the activation energy necessary for the reaction, and so promotes catalysis.

[2] For example, proteases such as chymotrypsin contain an oxyanion hole to stabilise the tetrahedral intermediate anion formed during proteolysis and protects substrate's negatively charged oxygen from water molecules.

[3] Additionally, it may allow for insertion or positioning of a substrate, which would suffer from steric hindrance if it could not occupy the hole (such as BPG in hemoglobin).

Oxyanion hole of a serine protease (black) stabilises negative charge build-up on the transition state of the substrate (red) using hydrogen bonds from enzyme's backbone amides (blue).