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Local binding with globally distributed changes in a small protease inhibitor upon enzyme binding
Author(s) -
Gáspári Zoltán,
Szenthe Borbála,
Patthy András,
Westler William M,
Gráf László,
Perczel András
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05204.x
Subject(s) - serine proteinase inhibitors , serine protease , protease inhibitor (pharmacology) , enzyme , chymotrypsin , protease , active site , enzyme inhibitor , chemistry , proteases , stereochemistry , serpin , serine , binding site , biochemistry , biology , trypsin , genetics , virus , antiretroviral therapy , viral load , gene
Complexation of the small serine protease inhibitor Schistocerca gregaria chymotrypsin inhibitor (SGCI), a member of the pacifastin inhibitor family, with bovine chymotrypsin was followed by NMR spectroscopy. 1 H– 15 N correlation (HSQC) spectra of the inhibitor with increasing amounts of the enzyme reveal tight and specific binding in agreement with biochemical data. Unexpectedly, and unparalleled among canonical serine protease inhibitors, not only residues in the protease‐binding loop of the inhibitor, but also some segments of it located spatially far from the substrate‐binding cleft of the enzyme were affected by complexation. However, besides changes, some of the dynamical features of the free inhibitor are retained in the complex. Comparison of the free and complexed inhibitor structures revealed that most, but not all, of the observed chemical shift changes can be attributed to minor structural transitions. We suggest that the classical ‘scaffold + binding loop’ model of canonical inhibitors might not be fully valid for the inhibitor family studied. In our view, this feature allows for the emergence of both taxon‐specific and nontaxon‐specific inhibitors in this group of small proteins.