2gab

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|PDB= 2gab |SIZE=350|CAPTION= <scene name='initialview01'>2gab</scene>, resolution 1.85&Aring;
|PDB= 2gab |SIZE=350|CAPTION= <scene name='initialview01'>2gab</scene>, resolution 1.85&Aring;
|SITE=
|SITE=
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|LIGAND= <scene name='pdbligand=NE2:3,3',4',5-TETRACHLOROBIPHENYL-4-OL'>NE2</scene>
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|LIGAND= <scene name='pdbligand=NE2:3,3&#39;,4&#39;,5-TETRACHLOROBIPHENYL-4-OL'>NE2</scene>
|ACTIVITY=
|ACTIVITY=
|GENE= TTR, PALB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
|GENE= TTR, PALB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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[[Category: ttr]]
[[Category: ttr]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:02:18 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 15:09:49 2008''

Revision as of 13:09, 23 March 2008

Image:2gab.gif


PDB ID 2gab

Drag the structure with the mouse to rotate
, resolution 1.85Å
Ligands:
Gene: TTR, PALB (Homo sapiens)
Coordinates: save as pdb, mmCIF, xml



Human Transthyretin (TTR) Complexed with Hydroxylated polychlorinated Biphenyl-4-hydroxy-3,3',5,4'-tetrachlorobiphenyl


Contents

Overview

Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) are known to bind to transthyretin (TTR) in vitro, possibly explaining their bioaccumulation, rodent toxicity, and presumed human toxicity. Herein, we show that several OH-PCBs bind selectively to TTR in blood plasma; however, only one of the PCBs tested binds TTR in plasma. Some of the OH-PCBs displace thyroid hormone (T4) from TTR, rationalizing the toxicity observed in rodents, where TTR is the major T4 transporter. Thyroid binding globulin and albumin are the major T4 carriers in humans, making it unlikely that enough T4 could be displaced from TTR to be toxic. OH-PCBs are excellent TTR amyloidogenesis inhibitors in vitro because they bind to the TTR tetramer, imparting kinetic stability under amyloidogenic denaturing conditions. Four OH-PCB/TTR cocrystal structures provide further insight into inhibitor binding interactions.

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

2GAB is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Hydroxylated polychlorinated biphenyls selectively bind transthyretin in blood and inhibit amyloidogenesis: rationalizing rodent PCB toxicity., Purkey HE, Palaninathan SK, Kent KC, Smith C, Safe SH, Sacchettini JC, Kelly JW, Chem Biol. 2004 Dec;11(12):1719-28. PMID:15610856

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