PDBsum entry 1o1v

Lipid binding protein

PDB id: 1o1v

Contents

Protein chain

127 a.a. *

Ligands

TCH

* Residue conservation analysis

PDB id:

1o1v

Name:

Lipid binding protein

Title:

Human ileal lipid-binding protein (ilbp) in complex with cholyltaurine

Structure:

Gastrotropin. Chain: a. Synonym: gt, ileal lipid-binding protein, ilbp, intestinal 15 kda protein, i-15p, intestinal bile acid-binding protein, i-babp. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fabp6 or illbp or ilbp. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

10 models

Authors:

M.Kurz,V.Brachvogel,H.Matter,S.Stengelin,H.Thuering,W.Kramer

Key ref:

M.Kurz et al. (2003). 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. PubMed id: 12486725 DOI: 10.1002/prot.10289

Date:

10-Feb-03 Release date: 18-Feb-03

Protein chain

P51161  (FABP6_HUMAN) -  Gastrotropin from Homo sapiens

Seq: 128 a.a.

Struc: 127 a.a.

DOI no: 10.1002/prot.10289

Proteins 50:312-328 (2003)

PubMed id: 12486725

Insights into the bile acid transportation system: the human ileal lipid-binding protein-cholyltaurine complex and its comparison with homologous structures.

M.Kurz, V.Brachvogel, H.Matter, S.Stengelin, H.Thüring, W.Kramer.

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.

Selected figure(s)

Figure 7.
Figure 7. A: Space-filling model of the human ILBP-cholyltaurine complex from restrained molecular dynamics and energy minimization. The structure is shown as ribbon-tube display of the backbone indicating secondary structure elements. B: Bile acid-binding cavity buried in the inner core of the human ILBP-cholyltaurine complex. The lipophilicity is mapped onto the solvent-accessible surface using the program MOLCAD. Z-clipping allows for a view into the interior, revealing the lipophilic bile acid-binding cavity (brown) in comparison with the outer ILBP surface. Blue areas indicate more polar outer surface areas, whereas a small channel is present at the upper left edge of the cavity. C: Detail about protein-ligand interactions. Only the solvent-accessible surface of the ILBP bile acid binding site is shown with lipophilicity mapped onto it. Only amino acids involved in intermolecular NOE interactions are displayed.

Figure 8.
Figure 8. Comparison of binding modes of cholyltaurine (white carbons) from the human ILBP complex and cholylglycine (green carbons) from the porcine ILBP complex. Only amino acids involved in intermolecular NOE interactions from the human ILBP structure and its solvent-accessible surface are shown. One representative cholylglycine conformation was extracted from the pdb file 1EIO after alignment of its backbone to the human ILBP structure described herein.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2003, 50, 312-328) copyright 2003.

Figures were selected by an automated process.