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Serpins: Finely Balanced Conformational Traps
Author(s) -
Pike Robert N.,
Bottomley Stephen P.,
Irving James A.,
Bird Phillip I.,
Whisstock James C.
Publication year - 2002
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216540213825
Subject(s) - serpin , proteases , serine protease , protease , serine , microbiology and biotechnology , intracellular , serine proteinase inhibitors , chemistry , function (biology) , biology , computational biology , biochemistry , enzyme , gene
Serine protease (serpins) play very important roles in the maintenance of various physiologically important systems. As knowledge of the workings of proteins of this family grows, new understanding is gained of the mechanisms by which they inhibit target proteases, using conformational changes for which the structure of serpins is uniquely adapted. This finely balanced system is utilized to healthy benefit in the control of serpin function by modulators, arguably the most striking examples of which occur in the control of proteolytic cascades, such as the coagulation system. Serpins also play very important intracellular roles: one example is the protection of immune cells from their own cytotoxic proteases. The finely balanced serpin mechanism also means that it is prone to disastrous consequences if mutations should occur in vital positions in the serpin structure. Many examples of disease‐associated mutations have been shown, which has the dual effect of highlighting how important these molecules are in the maintenance of health and the fine balance that must be maintained in order to preserve their active, inhibitory conformation.