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| | {{STRUCTURE_1tyr| PDB=1tyr | SCENE= }} | | {{STRUCTURE_1tyr| PDB=1tyr | SCENE= }} |
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| - | '''TRANSTHYRETIN COMPLEX WITH RETINOIC ACID'''
| + | ===TRANSTHYRETIN COMPLEX WITH RETINOIC ACID=== |
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| - | ==Overview==
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| - | Retinoids are quite insoluble and chemically unstable compounds in the aqueous medium, such that natural retinoids need to be bound to specific retinoid-binding proteins to be protected, solubilized and transported in body fluids. All-trans retinoic acid exhibits a relatively high affinity for thyroxine-binding transthyretin in vitro and this protein is a good candidate for the transport of retinoic acid administered as pharmacological or antitumor agent. To define structural features essential for the recognition by transthyretin of a ligand which is structurally unrelated to thyroxine, we have cocrystallized human transthyretin with retinoic acid and determined its structure at 0.18-nm resolution. The retinoid fits into the two chemically identical thyroxine-binding sites, which are located in the central channel that runs through the tetrameric transthyretin. The cyclohexene ring of the bound retinoid is innermost, occupying the same position of the phenolic ring of the bound 3,3'-diiodo-L-thyronine, whereas the carboxylate group, like the same group of the thyroid hormone, participates in an ionic interaction with the Lys15 side chain at the entrance of the channel. Despite the fact that transthyretin was cocrystallized with all-trans-retinoic acid, the isoprene chain of the bound retinoid has been found in a non-extended conformation. This feature, that allows the carboxylate to orient in a manner suitable for ion-pair association with the Lys15 side chain, is attributable to the conversion of all-trans-retinoic acid into cis-isomers or folded conformers. It is concluded that the presence, in an essentially hydrophobic molecular core of the appropriate size, of a negatively charged group at the correct position is a crucial requirement for ligand-transthyretin recognition. Whereas the binding of the ligand has no remarkable consequences for the protein structure, all-trans-retinoic acid undergoes structural changes such as to interact favorably with residues present in the thyroxine-binding sites, resembling roughly the natural ligand.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_8536704}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 8536704 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_8536704}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Zanotti, G.]] | | [[Category: Zanotti, G.]] |
| | [[Category: Retinol-binding protein]] | | [[Category: Retinol-binding protein]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:31:52 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 19:02:15 2008'' |
Revision as of 16:02, 28 July 2008
Template:STRUCTURE 1tyr
TRANSTHYRETIN COMPLEX WITH RETINOIC ACID
Template:ABSTRACT PUBMED 8536704
About this Structure
1TYR is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the transthyretin--retinoic-acid complex., Zanotti G, D'Acunto MR, Malpeli G, Folli C, Berni R, Eur J Biochem. 1995 Dec 1;234(2):563-9. PMID:8536704
Page seeded by OCA on Mon Jul 28 19:02:15 2008
