1gqf

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Revision as of 14:06, 20 November 2007

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spinqualitylabelsall models 1gqf, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF HUMAN PROCASPASE-7

Overview

Caspases form a family of proteinases required for the initiation and, execution phases of apoptosis. Distinct proapoptotic stimuli lead to, activation of the initiator caspases-8 and -9, which in turn activate the, common executioner caspases-3 and -7 by proteolytic cleavage. Whereas, crystal structures of several active caspases have been reported, no, three-dimensional structure of an uncleaved caspase zymogen is available, so far. We have determined the 2.9-A crystal structure of recombinant, human C285A procaspase-7 and have elucidated the activation mechanism of, caspases. The overall fold of the homodimeric procaspase-7 resembles that, of the active tetrameric caspase-7. Each monomer is organized in two, structured subdomains connected by partially flexible linkers, which, asymmetrically occupy and block the central cavity, a typical feature of, active caspases. This blockage is incompatible with a functional substrate, binding site/active site. After proteolytic cleavage within the flexible, linkers, the newly formed chain termini leave the cavity and fold outward, to form stable structures. These conformational changes are associated, with the formation of an intact active-site cleft. Therefore, this, mechanism represents a formerly unknown type of proteinase zymogen, activation.

About this Structure

1GQF is a Single protein structure of sequence from Homo sapiens with SO4 as ligand. Full crystallographic information is available from OCA.

Reference

Structural basis for the activation of human procaspase-7., Riedl SJ, Fuentes-Prior P, Renatus M, Kairies N, Krapp S, Huber R, Salvesen GS, Bode W, Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14790-5. PMID:11752425

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