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). Enzymes that catalyse multi-step reactions can have multiple oxyanion holes that stabilise different transition states in the reaction.^[4]

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).

See also

• Enzyme catalysis
• Active site
• Transition state
• Serine proteases#Catalytic mechanism