The Role of Structural Flexibility and Stability in the Interaction of Serine Proteases with their Inhibitors

Author(s): Laszlo Graf, Tamas Molnar, Jozsef Kardos, Zoltan Gaspari, Gergely Katona.

Journal Name: Current Protein & Peptide Science

Volume 16 , Issue 6 , 2015

Submit Manuscript
Submit Proposal

Graphical Abstract:


Abstract:

Serine proteases and their natural inhibitors have long been served as excellent models for studying (primary, secondary and tertiary) structure - activity relationships of biologically interacting proteins. As protein flexibility has been accepted as a “fourth dimension” of the protein structure, its contribution to the binding process has gained much interest. In this article we review extreme cases of serine protease interactions with canonical serine protease inhibitors that provide unique insights into the dynamics of protein- protein interactions. The major conclusions of our review article are: a) taxon-specific inhibitory effects of two highly homologous protease inhibitors from Schistocerca gregaria (SGCI and SGTI), as investigated by H/D exchange experiments and NMR spectroscopy, are due to their differential flexibilities, b) stabilities of some protease and inhibitor complexes, the wide-spread and increased flexibility of some segments in the protein-protein complexes, as studied by X-ray crystallography and NMR-spectroscopy, appear to be proportional to the physical stability of the complex.

Keywords: Canonical inhibitors, flexibility, protein-protein interactions, serine proteases, serpins, stability.

Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 16
ISSUE: 6
Year: 2015
Page: [521 - 531]
Pages: 11
DOI: 10.2174/1389203716666150429123733
Price: $58

Article Metrics

PDF: 25
HTML: 1
EPUB: 1