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1ezx
From Proteopedia
| 1ezx, resolution 2.60Å () | |||||
|---|---|---|---|---|---|
| Activity: | Trypsin, with EC number 3.4.21.4 | ||||
| Domains: | alpha-1-antitrypsin_like, Tryp_SPc | ||||
| |||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||
| Coordinates: | save as pdb, mmCIF, xml | ||||
CRYSTAL STRUCTURE OF A SERPIN:PROTEASE COMPLEX
The serpins have evolved to be the predominant family of serine-protease inhibitors in man. Their unique mechanism of inhibition involves a profound change in conformation, 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 A 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 activation. The disruption of the catalytic site prevents the release of the protease from the complex, and the structural disorder allows its proteolytic destruction. It is this ability of the conformational mechanism to crush as well as inhibit proteases that provides the serpins with their selective advantage.
Structure of a serpin-protease complex shows inhibition by deformation., Huntington JA, Read RJ, Carrell RW, Nature. 2000 Oct 19;407(6806):923-6. PMID:11057674
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1EZX is a Protein complex structure of sequences from Bos taurus and Homo sapiens. Additional information on 1EZX is available in a page on Serpins at the RCSB PDB Molecule of the Month. Full crystallographic information is available from OCA.
Reference
Structure of a serpin-protease complex shows inhibition by deformation., Huntington JA, Read RJ, Carrell RW, Nature. 2000 Oct 19;407(6806):923-6. PMID:11057674
Page seeded by OCA on Wed Jul 23 11:00:01 2008
