Saavedra et al. made mutants of the enzyme adenylate kinase, replacing non-glycine amino-acid residues with glycine residues at the surface of either the LID domain (red) or the AMPbd domain (blue). Both types of mutation caused local unfolding of the enzyme, increasing its disorder (entropy), and altered the enzyme’s functional behaviour, despite being distant from the active site. The LID mutations decreased the affinity of adenylate kinase for its substrates, whereas the AMPbd mutations increased the enzyme activity. Such entropic tuning of function might be an evolutionary mechanism that allows enzymes to cope with low temperatures, which usually slow enzymatic reactions.
This phenomenon might seem mysterious at first glance, but it is encapsulated in the idea of allosteric regulation — a common form of enzyme regulation in which the binding of a molecular partner at a site distant from the active site affects enzyme activity. The conventional view of allosteric regulation has been that binding of the partner causes small structural changes that propagate through the protein to alter the structure of the active site. However, there is now evidence for mechanisms involving changes in the dynamics (entropy), rather than in the structure, of the unbound state for many cases of allosteric regulation.
