9ETE

Crystal structure of recombinant chicken liver Bile Acid Binding Protein (cL-BABP) in complex with deoxycholic acid

9ETE の概要

• エントリーDOI: 10.2210/pdb9ete/pdb
• 関連するPDBエントリー: 9ETC 9ETD
• 分子名称: Fatty acid-binding protein, liver, (3ALPHA,5BETA,12ALPHA)-3,12-DIHYDROXYCHOLAN-24-OIC ACID (3 entities in total)
• 機能のキーワード: fatty acid binding protein, chicken liver bile acid binding protein, recombinant, bile acid, deoxycholic acid, lipid binding protein
• 由来する生物種: Gallus gallus (chicken)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30597.58

構造登録者

Tassone, G.,Pozzi, C. (登録日: 2024-03-26, 公開日: 2024-10-09)

主引用文献

Tassone, G.,Maramai, S.,Paolino, M.,Lamponi, S.,Poggialini, F.,Dreassi, E.,Petricci, E.,Alcaro, S.,Pozzi, C.,Romeo, I.
Exploiting the bile acid binding protein as transporter of a Cholic Acid/Mirin bioconjugate for potential applications in liver cancer therapy.
Sci Rep, 14:22514-22514, 2024

PubMed Abstract: Bioconjugation is one of the most promising strategies to improve drug delivery, especially in cancer therapy. Biomolecules such as bile acids (BAs) have been intensively explored as carriers, due to their peculiar physicochemical properties and biocompatibility. BAs trafficking is regulated by intracellular lipid-binding proteins and their transport in the liver can be studied using chicken liver Bile Acid-Binding Proteins (cL-BABPs) as a reference model. Therefore, we conceived the idea of developing a BA-conjugate with Mirin, an exonuclease inhibitor of Mre11 endowed with different anticancer activities, to direct its transport to the liver. Following computational analysis of various BAs in complex with cL-BABP, we identified cholic acid (CA) as the most promising candidate as carrier, leading to the synthesis of a novel bioconjugate named CA-M11. As predicted by computational data and confirmed by X-ray crystallographic studies, CA-M11 was able to accommodate into the binding pocket of BABP. Hence, it can enter BAs trafficking in the hepatic compartment and here release Mirin. The effect of CA-M11, evaluated in combination with varying concentrations of Doxorubicin on HepG2 cell line, demonstrated a significant increase in cell mortality compared to the use of the cytotoxic drug or Mirin alone, thus highlighting chemo-sensitizing properties. The promising results regarding plasma stability for CA-M11 validate its potential as a valuable agent or adjuvant for hepatic cancer therapy.

PubMed: 39341955
DOI: 10.1038/s41598-024-73636-w

実験手法

X-RAY DIFFRACTION (2.1 Å)