2K62

NMR solution structure of the supramolecular adduct between a liver cytosolic bile acid binding protein and a bile acid-based Gd(III)-chelate

2K62 の概要

• エントリーDOI: 10.2210/pdb2k62/pdb
• 関連するPDBエントリー: 2JN3
• NMR情報: BMRB: 15854
• 分子名称: Liver fatty acid-binding protein, YTTERBIUM (III) ION, (3alpha,5alpha,8alpha)-3-[(N,N-bis{2-[bis(carboxymethyl)amino]ethyl}-L-gamma-glutamyl)amino]cholan-24-oic acid (3 entities in total)
• 機能のキーワード: hepatospecific contrast agent, haddock, gd(iii) bile acid adduct, acetylation, cytoplasm, lipid-binding, transport, lipid binding protein
• 由来する生物種: Gallus gallus
• 細胞内の位置: Cytoplasm: P80226
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15096.20

構造登録者

Tomaselli, S.,Zanzoni, S.,Ragona, L.,Gianolio, E.,Aime, S.,Assfalg, M.,Molinari, H. (登録日: 2008-07-03, 公開日: 2008-11-04, 最終更新日: 2024-05-29)

主引用文献

Tomaselli, S.,Zanzoni, S.,Ragona, L.,Gianolio, E.,Aime, S.,Assfalg, M.,Molinari, H.
Solution structure of the supramolecular adduct between a liver cytosolic bile acid binding protein and a bile acid-based gadolinium(III)-chelate, a potential hepatospecific magnetic resonance imaging contrast agent.
J.Med.Chem., 51:6782-6792, 2008

PubMed Abstract: Bile acid-conjugated gadolinium chelates were shown to display promising features for the development of hepatospecific constrast agents for magnetic resonance imaging (MRI). The study of the pharmacokinetics of these compounds should address their possible interaction with the bile acid protein transporters. We have previously shown that a 5beta-cholanoic acid-based contrast agent is efficiently internalized in hepatocytes and is able to bind to a liver bile acid binding protein (BABP) in vitro. Here we report the solution structure of the adduct between a BABP and a gadolinium chelate/bile acid conjugate. The identification of unambiguous intermolecular distance restraints was possible through 3D edited/filtered NOESY-HSQC experiments, together with distance information derived from paramagnetic relaxation enhancements. These intermolecular contacts were used for the structure determination of the complex, using the data-driven docking software HADDOCK. The obtained results represent the starting point for the design of new and more efficient MRI contrast agents.

PubMed: 18939814
DOI: 10.1021/jm800820b

実験手法

SOLUTION NMR