2b15

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spinqualitylabelsall models 2b15, resolution 1.7Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

The crystal structure of 2,4-dinitrophenol in complex with human transthyretin

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Systemic deposition of transthyretin (TTR) amyloid fibrils is always, observed in familial amyloidotic polyneuropathy, senile systemic, amyloidosis and familial amyloidotic cardiomyopathy patients., Destabilization of the molecule leads to a cascade of events which result, in fibril formation. The destabilization of a native protein with, consequent conformational changes appears to be a common link in several, human amyloid diseases. Intensive research has been directed towards, finding small molecules that could work as therapeutic agents for the, prevention/inhibition of amyloid diseases through stabilization of the, native fold of the potentially amyloidogenic protein. This work provides, insight into the structural determinants of the highly stabilizing effects, of 2,4-dinitrophenol on wild-type TTR. It is also shown that similar, interactions are established between this molecule and two highly, amyloidogenic TTR variants: TTR L55P and TTR Y78F. In the three crystal, complexes, 2,4-dinitrophenol occupies the two hormone-binding sites of the, TTR tetramer. As a result of 2,4-dinitrophenol binding, the two dimers in, the TTR tetramer become closer, increasing the stability of the protein., The three-dimensional structures now determined allow a comprehensive, description of key interactions between transthyretin and, 2,4-dinitrophenol, a small compound that holds promise as a template for, the design of a therapeutical drug for amyloid diseases.

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

2B15 is a Single protein structure of sequence from Homo sapiens with SO4 and DNF as ligands. Full crystallographic information is available from OCA.

Reference

The binding of 2,4-dinitrophenol to wild-type and amyloidogenic transthyretin., Morais-de-Sa E, Neto-Silva RM, Pereira PJ, Saraiva MJ, Damas AM, Acta Crystallogr D Biol Crystallogr. 2006 May;62(Pt 5):512-9. Epub 2006, Apr 19. PMID:16627944

Page seeded by OCA on Mon Nov 12 20:57:02 2007