Chemical specificity and conformational flexibility in proteinase-inhibitor interaction: Scaffolds for promiscuous binding

One of the most important roles of proteins in cellular milieu is recognition of other biomolecules including other proteins. Protein-protein complexes are involved in many essential cellular processes. Interfaces of protein-protein complexes are traditionally known to be conserved in evolution and less flexible than other solvent interacting tertiary structural surface. But many examples are emerging where these features do not hold good. An understanding of inter-play between flexibility and sequence conservation is emerging, providing a fresh dimension to the paradigm of sequence-structure-function relationship. The functional manifestation of the inter-relation between sequence conservation and flexibility of interface is exemplified in this review using proteinase-inhibitor protein complexes.