The plasticity of the β-trefoil fold constitutes an evolutionary platform for protease inhibition.

TitleThe plasticity of the β-trefoil fold constitutes an evolutionary platform for protease inhibition.
Publication TypeJournal Article
Year of Publication2011
AuthorsAzarkan, M., S. Martinez-Rodriguez, L. Buts, D. Baeyens-Volant, and A. Garcia-Pino
JournalJ Biol Chem
Volume286
Issue51
Pagination43726-34
Date Published2011 Dec 23
ISSN1083-351X
KeywordsCarica, Chymotrypsin, Crystallography, X-Ray, Enzyme Inhibitors, Evolution, Molecular, Latex, Peptide Hydrolases, Protease Inhibitors, Protein Binding, Protein Folding, Protein Interaction Mapping, Protein Structure, Secondary, Protein Structure, Tertiary, Scattering, Radiation, Surface Plasmon Resonance, Trypsin
Abstract

Proteases carry out a number of crucial functions inside and outside the cell. To protect the cells against the potentially lethal activities of these enzymes, specific inhibitors are produced to tightly regulate the protease activity. Independent reports suggest that the Kunitz-soybean trypsin inhibitor (STI) family has the potential to inhibit proteases with different specificities. In this study, we use a combination of biophysical methods to define the structural basis of the interaction of papaya protease inhibitor (PPI) with serine proteases. We show that PPI is a multiple-headed inhibitor; a single PPI molecule can bind two trypsin units at the same time. Based on sequence and structural analysis, we hypothesize that the inherent plasticity of the β-trefoil fold is paramount in the functional evolution of this family toward multiple protease inhibition.

DOI10.1074/jbc.M111.291310
Alternate JournalJ. Biol. Chem.
PubMed ID22027836
PubMed Central IDPMC3243510