Enzyme Action: The Mechanism of Catalysis

An enzyme's ability to recognise and act on one particular substrate, out of the thousands of molecules present in a cell, depends on its active site -- a specific, often cleft-like or pocket-like region of the folded enzyme molecule, formed by amino acid residues that may lie far apart in the primary sequence but are brought close together by the enzyme's tertiary (or, for multi-subunit enzymes, quaternary) folding. Only a small number of amino acid residues within the active site are directly involved in binding the substrate and carrying out catalysis, but the correct three-dimensional shape of the entire folded protein is essential to holding these residues in exactly the right spatial arrangement.

When a substrate molecule binds to the active site, it forms a transient enzyme-substrate (ES) complex. Two classical models have been proposed to explain how this binding occurs. The lock-and-key model, proposed by Emil Fischer in 1894, pictures the active site as a rigid structure whose shape is precisely and permanently complementary to the shape of its substrate, in the same way that only one particular key will fit a given lock; this model neatly explains why a given enzyme is so specific for its substrate, but it does not easily account for the small conformational changes actually observed in many enzymes as they bind substrate. The induced-fit model, proposed by Daniel Koshland in 1958, instead pictures the active site as somewhat flexible, changing its shape slightly as the substrate approaches and binds, moulding itself around the substrate to achieve a closer, more precise fit -- rather like a glove adjusting to the shape of a hand as it is put on -- and this model better accounts both for enzyme specificity and for the small structural changes that accompany substrate binding. …