50th anniversary of the word "allosteric"

Abstract

A brief historical account on the origin and meaning of the word "allosteric" is presented. The word was coined in an attempt to qualify the chemical mechanism of the feedback inhibition of bacterial enzymes by regulatory ligands. The data lead to the proposal that, at variance with the classical mechanism of mutual exclusion by steric hindrance, the inhibition takes place through an "allosteric" interaction between "no overlapping", stereospecifically distinct, sites for substrate and feedback inhibitor, mediated by a discrete reversible alteration of the molecular structure of the protein.

Figure 1

Editorial note: The author kindly provided this photo of himself taken around 1965. I also thank Dr. Maurizio Brunori for suggesting this commemorative review. B.W.M.

Figure 2

Two alternate models were presented in my communication at the 1961 Cold Spring Harbor Symposium in Quantitative Biology to account for the effect of the feedback inhibition by L-isoleucine on the bacterial enzyme L-threonine deaminase. Model 1 represents the classical mechanism of mutual exclusion by steric hindrance. Model 2, with “no overlapping” of the substrate binding site and of the binding site of the feedback inhibitor was selected as the most adequate to account for the data. In the general discussion of the Symposium, Monod and Jacob coined the word “allosteric” to qualify this second model.