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The three-dimensional structures of complexes between bovine plasma
retinol-binding protein (RBP) and three retinol analogs with different end
groups (fenretinide, all-trans retinoic acid, and axerophthene) have been
determined to 1.8-1.9-A resolution. Their models are very similar to that of the
bovine retinol.RBP complex: the root mean square deviations between equivalent
alpha-carbons in the two proteins range from 0.17 to 0.24 A. The retinoid
molecules fit in the beta-barrel cavity assuming the same conformation of the
vitamin, and the substitutions have no consequences on the overall protein
structure. While confirming that an intact hydroxyl end group is not an absolute
requirement for a correct retinoid binding to RBP, this study has shown the
occurrence of conformational changes, although limited, in the rather flexible
loop region at the entrance of the beta-barrel upon fenretinide and retinoic
acid binding. These changes are suitable for accommodating the end groups of the
above retinoids. Instead, no such changes have been revealed in RBP complexed
with axerophthene, a retinol analog bearing a hydrogen atom in place of the
hydroxyl end group. The protein conformational changes in the above loop region,
the steric hindrance of bulky end groups of bound retinoids, and the lack of the
retinol hydroxyl group appear to be responsible for the possible reduced
affinity of retinoids for RBP relative to retinol and, at the same time, for the
abolished or reduced affinity of retinoid.RBP complexes for transthyretin
relative to retinol-RBP.
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