2gab
From Proteopedia
(New page: 200px<br /> <applet load="2gab" size="450" color="white" frame="true" align="right" spinBox="true" caption="2gab, resolution 1.85Å" /> '''Human Transthyretin...) |
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| - | [[Image:2gab.gif|left|200px]]<br /> | + | [[Image:2gab.gif|left|200px]]<br /><applet load="2gab" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2gab" size=" | + | |
caption="2gab, resolution 1.85Å" /> | caption="2gab, resolution 1.85Å" /> | ||
'''Human Transthyretin (TTR) Complexed with Hydroxylated polychlorinated Biphenyl-4-hydroxy-3,3',5,4'-tetrachlorobiphenyl'''<br /> | '''Human Transthyretin (TTR) Complexed with Hydroxylated polychlorinated Biphenyl-4-hydroxy-3,3',5,4'-tetrachlorobiphenyl'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2GAB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NE2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2GAB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NE2:'>NE2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GAB OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Kelly, J | + | [[Category: Kelly, J W.]] |
| - | [[Category: Palaninathan, S | + | [[Category: Palaninathan, S K.]] |
| - | [[Category: Sacchettini, J | + | [[Category: Sacchettini, J C.]] |
| - | [[Category: Safe, S | + | [[Category: Safe, S H.]] |
[[Category: Smith, C.]] | [[Category: Smith, C.]] | ||
[[Category: NE2]] | [[Category: NE2]] | ||
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[[Category: ttr]] | [[Category: ttr]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:29:42 2008'' |
Revision as of 15:29, 21 February 2008
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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 with as ligand. 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
Page seeded by OCA on Thu Feb 21 17:29:42 2008
Categories: Homo sapiens | Single protein | Kelly, J W. | Palaninathan, S K. | Sacchettini, J C. | Safe, S H. | Smith, C. | NE2 | Amyloid | Transthyretin | Ttr
