Chemical Specificity and Conformational Flexibility in Proteinase-Inhibitor Interaction: Scaffolds for Promiscuous Binding

Prog Biophys Mol Biol. Nov-Dec 2014;116(2-3):151-7. doi: 10.1016/j.pbiomolbio.2014.08.003. Epub 2014 Aug 20.

Abstract

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.

Keywords: Interface flexibility; Promiscuous binding; Proteinase inhibitors; Proteinases; Protein–protein interaction; Sequence variability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Peptide Hydrolases / chemistry*
  • Peptide Hydrolases / metabolism*
  • Protease Inhibitors / metabolism*
  • Protease Inhibitors / pharmacology*
  • Protein Binding
  • Protein Conformation
  • Protein Engineering
  • Substrate Specificity

Substances

  • Protease Inhibitors
  • Peptide Hydrolases