Review Co-operative and allosteric enzymes: 20 years on

The concepts of co-operativity and allosteric behaviour in proteins have been commonplace in biochemistry for about 20 years, since the classic papers of Monod, Wyman and Changeux [l] and Koshland, Nkmethy and Filmer [2]. None-theless, the two terms are not always clearly distinguished or used consistently, and in any case the definitions that were appropriate originally may not still be so today. So we should begin by defining what we mean by co-operative and allosteric behaviour. Co-operativity in relation to the Adair scheme In the strictest sense, co-operativity can only be displayed by a binding system at equilibrium, but even then there are two possibilities that are not equivalent. First, one can adopt a purely mechanistic approach and consider co-operativity in relation to the Adair scheme, first proposed by Adair [3] in relation to the binding of oxygen to haemoglobin. If a ligand X binds successively to n sites on a protein E with association constants K,, K2, K3... Kn, the process can be represented as follows: E + X = E X; K1 = lEXl/n[EI[X