1ezx

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spinqualitylabelsall models 1ezx, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF A SERPIN:PROTEASE COMPLEX

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Emphysema OMIM:[107400], Emphysema-cirrhosis OMIM:[107400], Hemorrhagic diathesis due to antithrombin Pittsburgh OMIM:[107400], Pulmonary disease, chronic obstructive, susceptibility to OMIM:[107400]

About this Structure

1EZX is a Protein complex structure of sequences from Bos taurus and Homo sapiens. The following page contains interesting information on the relation of 1EZX with [Serpins]. Active as Trypsin, with EC number 3.4.21.4 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 Mon Nov 12 16:47:54 2007