1O1V

Human Ileal Lipid-Binding Protein (ILBP) in Complex with Cholyltaurine

1O1V の概要

• エントリーDOI: 10.2210/pdb1o1v/pdb
• 関連するPDBエントリー: 1O1U
• 分子名称: Gastrotropin, TAUROCHOLIC ACID (2 entities in total)
• 機能のキーワード: beta clam structure, lipid binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform 1: Cytoplasm. Isoform 2: Cytoplasm: P51161
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14773.74

構造登録者

Kurz, M.,Brachvogel, V.,Matter, H.,Stengelin, S.,Thuering, H.,Kramer, W. (登録日: 2003-02-10, 公開日: 2003-02-18, 最終更新日: 2023-12-27)

主引用文献

Kurz, M.,Brachvogel, V.,Matter, H.,Stengelin, S.,Thuering, H.,Kramer, W.
Insights into the bile acid transportation system: the human ileal lipid-binding protein-cholyltaurine complex and its comparison with homologous structures.
Proteins, 50:312-328, 2003

PubMed Abstract: Bile acids are generated in vivo from cholesterol in the liver, and they undergo an enterohepatic circulation involving the small intestine, liver, and kidney. To understand the molecular mechanism of this transportation, it is essential to gain insight into the three-dimensional (3D) structures of proteins involved in the bile acid recycling in free and complexed form and to compare them with homologous members of this protein family. Here we report the solution structure of the human ileal lipid-binding protein (ILBP) in free form and in complex with cholyltaurine. Both structures are compared with a previously published structure of the porcine ILBP-cholylglycine complex and with related lipid-binding proteins. Protein structures were determined in solution by using two-dimensional (2D)- and 3D-homo and heteronuclear NMR techniques, leading to an almost complete resonance assignment and a significant number of distance constraints for distance geometry and restrained molecular dynamics simulations. The identification of several intermolecular distance constraints unambiguously determines the cholyltaurine-binding site. The bile acid is deeply buried within ILBP with its flexible side-chain situated close to the fatty acid portal as entry region into the inner ILBP core. This binding mode differs significantly from the orientation of cholylglycine in porcine ILBP. A detailed analysis using the GRID/CPCA strategy reveals differences in favorable interactions between protein-binding sites and potential ligands. This characterization will allow for the rational design of potential inhibitors for this relevant system.

PubMed: 12486725
DOI: 10.1002/prot.10289

実験手法

SOLUTION NMR