2h4e

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spinqualitylabelsall models 2h4e, resolution 1.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of Cys10 sulfonated transthyretin

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Transthyretin (TTR) is a plasma protein, which under conditions not yet, completely understood, aggregates forming amyloid deposits that occur, extracellularly. It is a protein composed of four identical subunits. Each, monomer has a single cysteine residue (Cys10), which in the plasma is, reduced (Cys-SH), oxidized (Cys-SO3-), sulfonated (Cys-S-SO3-) or bound to, various sulfhydryls. There is evidence that these chemical modifications, of the SH group alter the stability and the amyloidogenic potential of the, protein. The sulfonated form was found to enhance the stability of the, native conformation of TTR, avoiding misassembly of the protein leading to, amyloid. Consequently, the potential treatment of TTR-type amyloidosis by, sulfite has been suggested. The structure of TTR pre-incubated with, sulfite at physiological pH, was determined by X-ray crystallography to, provide structural insight for the stabilizing effect of sulfite. Each, subunit has a beta-sandwich conformation, with two four stranded, beta-pleated sheets (DAGH and CBEF) and a small alpha-helix between, strands. The sulfonated cysteines have two sulfite oxygens involved in, intramonomer hydrogen bonds that bridge Cys10, the amino acid immediately, before beta-strand A, to the amino acids immediately after the edge, beta-strand D. Implications of the newly observed interactions in the, inhibition of fibril formation are discussed in light of the recent, structural models of TTR amyloid fibrils.

Disease

Known diseases associated with this structure: Amyloid neuropathy, familial, several allelic types OMIM:[176300], Amyloidosis, senile systemic OMIM:[176300], Carpal tunnel syndrome, familial OMIM:[176300], Dystransthyretinemic hyperthyroxinemia OMIM:[176300]

About this Structure

2H4E 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 protective role of sulfite against transthyretin amyloid formation., Gales L, Saraiva MJ, Damas AM, Biochim Biophys Acta. 2007 Jan;1774(1):59-64. Epub 2006 Nov 6. PMID:17175208

Page seeded by OCA on Mon Nov 12 22:26:12 2007