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The many faces of protease–protein inhibitor interaction
Author(s) -
Otlewski Jacek,
Jelen Filip,
Zakrzewska Malgorzata,
Oleksy Arkadiusz
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600611
Subject(s) - biology , protease , protease inhibitor (pharmacology) , computational biology , microbiology and biotechnology , biochemistry , genetics , enzyme , virus , viral load , antiretroviral therapy
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.