1tyr: Difference between revisions
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'''TRANSTHYRETIN COMPLEX WITH RETINOIC ACID''' | {{Structure | ||
|PDB= 1tyr |SIZE=350|CAPTION= <scene name='initialview01'>1tyr</scene>, resolution 1.8Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=REA:RETINOIC ACID'>REA</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''TRANSTHYRETIN COMPLEX WITH RETINOIC ACID''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1TYR is a [ | 1TYR is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TYR OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/8536704 8536704] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: retinol-binding protein]] | [[Category: retinol-binding protein]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:24:58 2008'' | ||
Revision as of 15:24, 20 March 2008
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
TRANSTHYRETIN COMPLEX WITH RETINOIC ACID
OverviewOverview
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.
DiseaseDisease
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 StructureAbout this Structure
1TYR is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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
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