title: Crystal structures of cellular retinoic acid binding proteins I and II in complex with all-trans-retinoic acid and a synthetic retinoid.
abstract: BACKGROUND
  Retinoic acid (RA) plays a fundamental role in diverse cellular activities. Cellular RA binding proteins (CRABPs) are thought to act by modulating the amount of RA available to nuclear RA receptors. CRABPs and cellular retinol-binding proteins (CRBPs) share a unique fold of two orthogonal beta-sheets that encapsulate their ligands. It has been suggested that a trio of residues are the prime determinants defining the high specificity of CRBPs and CRABPs for their physiological ligands.
  
  
  RESULTS
  Bovine/murine CRABP I and human CRABP II have been crystallized in complex with their natural ligand, all-trans-RA. Human CRABP II has also been crystallized in complex with a synthetic retinoid, 'compound 19'. Their structures have been determined and refined at resolutions of 2.9 A, 1.8 A and 2.2 A, respectively.
  
  
  CONCLUSIONS
  The retinoid-binding site in CRABPs differs significantly from that observed in CRBP. Structural changes in three juxtaposed areas of the protein create a new, displaced binding site for RA. The carboxylate of the ligand interacts with the expected trio of residues (Arg132, Tyr134 and Arg111; CRABP II numbering). The RA ligand is almost flat with the beta-ionone ring showing a significant deviation (-33 degrees) from a cis conformation relative to the isoprene tail. The edge atoms of the beta-ionone ring are accessible to solvent in a suitable orientation for presentation to metabolizing enzymes. The bulkier synthetic retinoid causes small conformational changes in the protein structure.
authors.affiliation: Department of Molecular Biology, Uppsala University, Sweden.
authors.forename: G J
authors.initials: GJ
authors.lastname: Kleywegt
authors.forename: T
authors.initials: T
authors.lastname: Bergfors
authors.forename: H
authors.initials: H
authors.lastname: Senn
authors.forename: P
authors.initials: P
authors.lastname: Le Motte
authors.forename: B
authors.initials: B
authors.lastname: Gsell
authors.forename: K
authors.initials: K
authors.lastname: Shudo
authors.forename: T A
authors.initials: TA
authors.lastname: Jones
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D011487:Protein Conformation; D018168:Receptors, Retinoic Acid / Q000737:chemistry*; D012176:Retinoids / Q000737:chemistry*; D014212:Tretinoin / Q000737:chemistry*
chemical_list: D008024:Ligands; D018168:Receptors, Retinoic Acid; D012176:Retinoids; C082927:retinoic acid binding protein I, cellular; C082928:retinoic acid binding protein II, cellular; D014212:Tretinoin