Crystal structure of chicken liver basic fatty acid-binding protein complexed with cholic acid

Biochemistry. 2004 Nov 9;43(44):14072-9. doi: 10.1021/bi0489661.

Abstract

Two paralogous groups of liver fatty acid-binding proteins (FABPs) have been described: the mammalian type liver FABPs and the basic type (Lb-FABPs) characterized in several vertebrates but not in mammals. The two groups have similar sequences and share a highly conserved three-dimensional structure, but their specificity and stoichiometry of binding are different. The crystal structure of chicken Lb-FABP complexed with cholic acid and that of the apoprotein refined to 2.0 A resolution are presented in this paper. The two forms of the protein crystallize in different space groups, and significant changes are observed between the two conformations. The holoprotein binds two molecules of cholate in the interior cavity, and the contacts observed between the two ligands can help to explain the reason for this stoichiometry of binding. Most of the amino acids involved in ligand binding are conserved in other members of the Lb-FABP family. Since the amino acid sequence of the Lb-FABPs is more similar to that of the bile acid-binding proteins than to that of the L-FABPs, the possibility that the Lb-FABPs might be more appropriately called liver bile acid-binding proteins (L-BABPs) is suggested.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoproteins / chemistry
  • Apoproteins / metabolism
  • Bile Acids and Salts / chemistry
  • Bile Acids and Salts / metabolism
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Chickens
  • Cholic Acid / chemistry*
  • Cholic Acid / metabolism
  • Conserved Sequence
  • Crystallization
  • Crystallography, X-Ray* / methods
  • Fatty Acid-Binding Proteins
  • Ligands
  • Liver / chemistry*
  • Liver / metabolism*
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation

Substances

  • Apoproteins
  • Bile Acids and Salts
  • Carrier Proteins
  • Fatty Acid-Binding Proteins
  • Ligands
  • Membrane Glycoproteins
  • bile acid binding proteins
  • Cholic Acid

Associated data

  • PDB/1TVQ
  • PDB/1TW4