The role of structural flexibility and stability in the interaction of serine proteases with their inhibitors.

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.

journal_name

Curr Protein Pept Sci

authors

Gráf L,Molnár T,Kardos J,Gáspári Z,Katona G

doi

10.2174/1389203716666150429123733

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

521-31

issue

6

eissn

1389-2037

issn

1875-5550

pii

CPPS-EPUB-66906

journal_volume

16

pub_type

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