EconPapers    
Economics at your fingertips  
 

Structure of a serpin–protease complex shows inhibition by deformation

James A. Huntington (), Randy J. Read and Robin W. Carrell
Additional contact information
James A. Huntington: University of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research
Randy J. Read: University of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research
Robin W. Carrell: University of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research

Nature, 2000, vol. 407, issue 6806, 923-926

Abstract: Abstract The serpins have evolved to be the predominant family of serine-protease inhibitors in man1,2. Their unique mechanism of inhibition involves a profound change in conformation3, although the nature and significance of this change has been controversial. Here we report the crystallographic structure of a typical serpin–protease complex and show the mechanism of inhibition. The conformational change is initiated by reaction of the active serine of the protease with the reactive centre of the serpin. This cleaves the reactive centre, which then moves 71 Å to the opposite pole of the serpin, taking the tethered protease with it. The tight linkage of the two molecules and resulting overlap of their structures does not affect the hyperstable serpin, but causes a surprising 37% loss of structure in the protease. This is induced by the plucking of the serine from its active site, together with breakage of interactions formed during zymogen activation4. The disruption of the catalytic site prevents the release of the protease from the complex, and the structural disorder allows its proteolytic destruction5,6. It is this ability of the conformational mechanism to crush as well as inhibit proteases that provides the serpins with their selective advantage.

Date: 2000
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/35038119 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:407:y:2000:i:6806:d:10.1038_35038119

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/35038119

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().

 
Page updated 2025-03-19
Handle: RePEc:nat:nature:v:407:y:2000:i:6806:d:10.1038_35038119