2g5u

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{{STRUCTURE_2g5u| PDB=2g5u | SCENE= }}
{{STRUCTURE_2g5u| PDB=2g5u | SCENE= }}
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'''Human Transthyretin (TTR) Complexed with Hydroxylated polychlorinated Biphenyl-4,4'-dihydroxy-3,3',5,5'-tetrachlorobiphenyl'''
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===Human Transthyretin (TTR) Complexed with Hydroxylated polychlorinated Biphenyl-4,4'-dihydroxy-3,3',5,5'-tetrachlorobiphenyl===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_15610856}}
==About this Structure==
==About this Structure==
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[[Category: Transthyretin]]
[[Category: Transthyretin]]
[[Category: Ttr]]
[[Category: Ttr]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:43:17 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 16:05:06 2008''

Revision as of 13:05, 27 July 2008

Image:2g5u.png

Template:STRUCTURE 2g5u

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

Template:ABSTRACT PUBMED 15610856

About this Structure

2G5U 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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