1e4h
From Proteopedia
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==Overview== | ==Overview== | ||
The binding of two organohalogen substances, pentabromophenol (PBP) and, 2,4,6-tribromophenol (TBP), to human transthyretin (TTR), a thyroid, hormone transport protein, has been studied by in vitro competitive, binding assays and by X-ray crystallography. Both compounds bind to TTR, with high affinity, in competition with the natural ligand thyroxine, (T(4)). The crystal structures of the TTR-PBP and TTR-TBP complexes show, some unusual binding patterns for the ligands. They bind exclusively in, the 'reversed' mode, with their hydroxyl group pointing towards the mouth, of the binding channel and in planes approximately perpendicular to that, adopted by the T(4) phenolic ring in a TTR-T(4) complex, a feature not, observed before. The hydroxyl group in the ligands, which was previously, thought to be a key ingredient for a strong binding to TTR, does not seem, to play an important role in the binding of these compounds to TTR. In the, TTR-PBP complex, it is primarily the halogens which interact with the TTR, molecule and therefore must account for the strong affinity of binding., The interactions with the halogens are smaller in number in TTR-TBP and, there is a decrease in affinity, even though the interaction with the, hydroxyl group is stronger than that in the TTR-PBP complex. | The binding of two organohalogen substances, pentabromophenol (PBP) and, 2,4,6-tribromophenol (TBP), to human transthyretin (TTR), a thyroid, hormone transport protein, has been studied by in vitro competitive, binding assays and by X-ray crystallography. Both compounds bind to TTR, with high affinity, in competition with the natural ligand thyroxine, (T(4)). The crystal structures of the TTR-PBP and TTR-TBP complexes show, some unusual binding patterns for the ligands. They bind exclusively in, the 'reversed' mode, with their hydroxyl group pointing towards the mouth, of the binding channel and in planes approximately perpendicular to that, adopted by the T(4) phenolic ring in a TTR-T(4) complex, a feature not, observed before. The hydroxyl group in the ligands, which was previously, thought to be a key ingredient for a strong binding to TTR, does not seem, to play an important role in the binding of these compounds to TTR. In the, TTR-PBP complex, it is primarily the halogens which interact with the TTR, molecule and therefore must account for the strong affinity of binding., The interactions with the halogens are smaller in number in TTR-TBP and, there is a decrease in affinity, even though the interaction with the, hydroxyl group is stronger than that in the TTR-PBP complex. | ||
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Amyloid neuropathy, familial, several allelic types OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176300 176300]], Amyloidosis, senile systemic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176300 176300]], Carpal tunnel syndrome, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176300 176300]], Dystransthyretinemic hyperthyroxinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176300 176300]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: transport(thyroxine)]] | [[Category: transport(thyroxine)]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:39:40 2007'' |
Revision as of 14:33, 12 November 2007
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STRUCTURE OF HUMAN TRANSTHYRETIN COMPLEXED WITH BROMOPHENOLS: A NEW MODE OF BINDING
Contents |
Overview
The binding of two organohalogen substances, pentabromophenol (PBP) and, 2,4,6-tribromophenol (TBP), to human transthyretin (TTR), a thyroid, hormone transport protein, has been studied by in vitro competitive, binding assays and by X-ray crystallography. Both compounds bind to TTR, with high affinity, in competition with the natural ligand thyroxine, (T(4)). The crystal structures of the TTR-PBP and TTR-TBP complexes show, some unusual binding patterns for the ligands. They bind exclusively in, the 'reversed' mode, with their hydroxyl group pointing towards the mouth, of the binding channel and in planes approximately perpendicular to that, adopted by the T(4) phenolic ring in a TTR-T(4) complex, a feature not, observed before. The hydroxyl group in the ligands, which was previously, thought to be a key ingredient for a strong binding to TTR, does not seem, to play an important role in the binding of these compounds to TTR. In the, TTR-PBP complex, it is primarily the halogens which interact with the TTR, molecule and therefore must account for the strong affinity of binding., The interactions with the halogens are smaller in number in TTR-TBP and, there is a decrease in affinity, even though the interaction with the, hydroxyl group is stronger than that in the TTR-PBP complex.
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
1E4H is a Single protein structure of sequence from Homo sapiens with PBR and GOL as ligands. Structure known Active Sites: AC1 and AC2. Full crystallographic information is available from OCA.
Reference
Structure of human transthyretin complexed with bromophenols: a new mode of binding., Ghosh M, Meerts IA, Cook A, Bergman A, Brouwer A, Johnson LN, Acta Crystallogr D Biol Crystallogr. 2000 Sep;56(Pt 9):1085-95. PMID:10957627
Page seeded by OCA on Mon Nov 12 16:39:40 2007
