1o1u: Difference between revisions

Revision as of 15:12, 21 February 2008

human ileal lipid-binding protein (ILBP) in free form

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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 ==Overview==
-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.
+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 Structure==
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 [[Category: beta clam structure]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:31:52 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:12:25 2008''