NMR study of the binding of all-trans-retinoic acid to type II human cellular retinoic acid binding protein.
Cellular RA binding proteins are thought to play important roles in the (RA), a hormonally active metabolite of vitamin A that has profound effects on cell growth, + differentiation and morphogenesis. Binding of RA to type II human cellular RA binding proteins (CRABPII) has been investigated by NMR spectroscopy. The sequential resonance assignments of +CRABPII in the presence of RA were established by heteronuclear three-dimensional NMR at pH 7.3. The resonance assignments of the bound RA were achieved by homonucl NMR. The secondary structures of holo-CRABPII determined by NMR were ess as revealed by the crystal structure of holo-CRABPII. Most of the nuclear Overhauser effects (NOEs) between CRABPII and the bound RA were consistent with those predicted crystal structure of holo-CRABPII. The results suggested that the conformations in solution and in the crystalline state are highly similar. Compared to the ligand binding pocket, especially the ligand entrance, was stabilize Ser12-Leu18, one of the structure elements that constitute the ligand binding pocket, became more mobile upon binding of RA. Intramolecular NOEs between protons of the bo the carboxylate end of the bound RA is well fixed but the &beta;-ionone
Wang
L
L
Department of Biochemistry, Michigan State University, East Lansing, MI 48824, USA.
Yan
H
H
D000595:Amino Acid Sequence; D003460:Crystallization; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008969:Molecular Sequence Data; D011487:Protein Conformation / Q000187:drug effects; D018168:Receptors, Retinoic Acid / Q000737:chemistry* / Q000378:metabolism; D012996:Solutions; D014212:Tretinoin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
D018168:Receptors, Retinoic Acid; D012996:Solutions; C082928:retinoic acid binding protein II, cellular; D014212:Tretinoin