1o1u
human ileal lipid-binding protein (ILBP) in free form
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OverviewOverview
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.
About this StructureAbout this Structure
1O1U is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Insights into the bile acid transportation system: the human ileal lipid-binding protein-cholyltaurine complex and its comparison with homologous structures., Kurz M, Brachvogel V, Matter H, Stengelin S, Thuring H, Kramer W, Proteins. 2003 Feb 1;50(2):312-28. PMID:12486725
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