I t is well known that domains are the fundamental units of tertiary structure of proteins.
Domains are also units of function, each domain being associated with a specific functionality.
In an attempt to design new proteins having the functionality of both parent molecules, the authors have engineered chimeric interleukins in which the inhibitory loop from several proteinase inhibitors was transplanted. Serine proteinase inhibitors interact with their cognate enzymes via an external loop that has a canonical conformation in all known inhibitors. Moreover, the chosen region was not involved in interleukin receptor recognition. The chimeric interleukins were then tested for both their inhibitory activity and interleukin receptor binding. The mutants containing the inhibitory loop of alpha1-Proteinase Inhibitor or STI displayed significant inhibition of elastase, chymotrypsin or trypsin and still exhibited cytokine activities.