Introductory lecture: what are enzyme structures telling us?

Abstract

Most globular proteins are waxy inside and soapy outside. Their compact structures are stabilised by the hydrophobic effect which is mainly entropic, and by hydrogen bonds and dispersion forces which are mainly enthalpic. Structurally homologous proteins tend to share a common set of internal sites from which polar residues are excluded, even if they share little sequence homology.

Electrostatic effects are dominant in enzyme catalysis. The active sites of enzymes are generally buried in clefts or cavities where dipoles tend to be oriented so as to optimise the pK_as of ionizable amino acid side chains for catalysis; substrates are clamped close by to maximise electrostatic interactions.

The activities of many enzymes have long been known to be controlled by allosteric effects or by induced fit. Some serine proteinase inhibitors have evolved yet another control mechanism: this is a spring-loaded safety catch that makes them revert to their latent, stable, inactive form unless the catch is kept in the ‘loaded’ position by another molecule.