The many faces of protease-protein inhibitor interaction.
Proteases and their natural protein inhibitors are among the most intensively studied protein-protein complexes. There are about 30 structurally distinct inhibitor families that are able to block serine, cysteine, metallo- and aspartyl proteases. The mechanisms of inhibition can be related to the catalytic mechanism of protease action or include a mechanism-unrelated steric blockage of the active site or its neighborhood. The structural elements that are responsible for the inhibition most often include the N- or the C-terminus or exposed loop(s) either separately or in combination of several such elements. During complex formation, no major conformational changes are usually observed, but sometimes structural transitions of the inhibitor and enzyme occur. In many cases, convergent evolution, with respect to the inhibitors' parts that are responsible for the inhibition, can be inferred from comparisons of their structures or sequences, strongly suggesting that there are only limited ways to inhibit proteases by proteins.
Otlewski
Jacek
J
Institute of Biochemistry and Molecular Biology, University of Wroclaw, Wroclaw, Poland. otlewski@protein.pl
Jelen
Filip
F
Zakrzewska
Malgorzata
M
Oleksy
Arkadiusz
A
D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D002384:Catalysis; D019143:Evolution, Molecular; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D046912:Multiprotein Complexes; D011506:Proteins; D010447:Peptide Hydrolases