2ch9

From Proteopedia

Revision as of 16:03, 5 November 2007

CRYSTAL STRUCTURE OF DIMERIC HUMAN CYSTATIN F

Overview

Cystatins are important natural cysteine protease inhibitors targeting, primarily papain-like cysteine proteases, including cathepsins and, parasitic proteases like cruzipain, but also mammalian asparaginyl, endopeptidase. Mammalian cystatin F, which is expressed almost exclusively, in hematopoietic cells and accumulates in lysosome-like organelles, has, been implicated in the regulation of antigen presentation and other immune, processes. It is an unusual cystatin superfamily member with a, redox-regulated activation mechanism and a restricted specificity profile., We describe the 2.1A crystal structure of human cystatin F in its dimeric, "off" state. The two monomers interact in a fashion not seen before for, cystatins or cystatin-like proteins that is crucially dependent on an, unusual intermolecular disulfide bridge, suggesting how reduction leads to, monomer formation and activation. Strikingly, core sugars for one of the, two N-linked glycosylation sites of cystatin F are well ordered, and their, conformation and interactions with the protein indicate that this unique, feature of cystatin F may modulate its inhibitory properties, in, particular its reduced affinity toward asparaginyl endopeptidase compared, with other cystatins.

About this Structure

2CH9 is a Single protein structure of sequence from Homo sapiens with NAG, ZN and ACT as ligands. Structure known Active Site: AC6. Full crystallographic information is available from OCA.

Reference

Structural basis of reduction-dependent activation of human cystatin F., Schuttelkopf AW, Hamilton G, Watts C, van Aalten DM, J Biol Chem. 2006 Jun 16;281(24):16570-5. Epub 2006 Apr 6. PMID:16601115

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