The role of structural flexibility and stability in the interaction of serine proteases with their inhibitors.
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.
Department of Biochemistry, Eötvös Loránd University, P.O. Box: 1117, Budapest, Hungary. graf@elte.hu.
László
L
Gráf
Tamás
T
Molnár
József
J
Kardos
Zoltán
Z
Gáspári
Gergely
G
Katona
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D016415:Sequence Alignment; D057057:Serine Proteases / Q000737:chemistry*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry*; D013329:Structure-Activity Relationship
D015842:Serine Proteinase Inhibitors; D057057:Serine Proteases