1TYR

TRANSTHYRETIN COMPLEX WITH RETINOIC ACID

1TYR の概要

• エントリーDOI: 10.2210/pdb1tyr/pdb
• 関連するPDBエントリー: 2PAB
• 分子名称: TRANSTHYRETIN, (9cis)-retinoic acid (3 entities in total)
• 機能のキーワード: retinol-binding protein, retinol-binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P02766
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28155.59

構造登録者

Zanotti, G.,D'Acunto, M.R.,Malpeli, G.,Folli, C.,Berni, R. (登録日: 1995-05-12, 公開日: 1995-09-15, 最終更新日: 2024-12-25)

主引用文献

Zanotti, G.,D'Acunto, M.R.,Malpeli, G.,Folli, C.,Berni, R.
Crystal structure of the transthyretin--retinoic-acid complex
Eur.J.Biochem., 234:563-569, 1995

PubMed Abstract: 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.

PubMed: 8536704
DOI: 10.1111/j.1432-1033.1995.563_b.x

実験手法

X-RAY DIFFRACTION (1.8 Å)