Citation

Engh RA, Huber R, Bode W, Schulze AJ. Trends Biotechnol. 1995; 13(12): 503-510.

Copyright

(Copyright © 1995, Elsevier Publishing)

DOI

10.1016/S0167-7799(00)89013-7

PMID

8595135

Abstract

The most important of diverse serpin functions is serine-protease inhibition. In contrast to the 'standard-mechanism' inhibitors, inhibitory serpins use a mechanism that involves unusual flexibility, and cofactor and receptor interactions. The principal feature is a refolding step, during which a disordered or helical strand is inserted into the center of a beta sheet. This transition, which is essential for inhibition, can be induced by heating, proteolytic cleavage of the serpin, or complexation with the proteinase target; analogous transitions can be induced by peptide complexation or aggregation. Although it is difficult to determine the details of this mechanism, information derived from crystal structures and other experiments has stimulated drug design efforts with wide-ranging potential applications.

Language: en

Keywords

Crystallography, X-Ray; Forecasting; Humans; Models, Biological; Models, Molecular; Ovalbumin; Plasminogen Activator Inhibitor 1; Protein Conformation; Protein Engineering; Protein Folding; Serine Proteinase Inhibitors; Serpins