NMR studies of retinoid-protein interactions: the conformation of [13C]-beta-ionones
 

NMR studies of retinoid-protein interactions: the conformation of [13C]-beta-ionones bound to beta-lactoglobulin B.

Related Articles NMR studies of retinoid-protein interactions: the conformation of [13C]-beta-ionones bound to beta-lactoglobulin B.

Pharm Res. 1999 May;16(5):651-9

Authors: Curley RW, Sundaram AK, Fowble JW, Abildgaard F, Westler WM, Markley JL

PURPOSE: Vitamin A (retinol) and its metabolites comprise the natural retinoids. While the biological action of these molecules are thought to be primarily mediated by ca. 55 kDa nuclear retinoic acid receptors, a number of structurally similar 15-20 kDa proteins are involved in the transport, and possibly metabolism, of these compounds. The milk protein beta-lactoglobulin B (beta-LG) is an 18 kDa protein which binds retinol and may be involved in oral delivery of retinol to neonates. beta-LG also binds drugs and other natural products and is of potential interest as a protective delivery vehicle. METHODS: To examine the conformation of the model retinoid beta-ionone both in solution and when bound to beta-LG, NMR and computational methods have been employed. RESULTS: Taken together, NMR studies of beta-ionone in solution measuring scalar and dipolar coupling, as well as CHARMm calculations, suggest beta-ionone prefers a slightly twisted 6-s-cis conformation. Isotope-edited NMR studies of 13C-labeled beta-ionones bound to beta-LG, primarily employing the HMQC-NOE experiment, suggest beta-ionone also binds to beta-LG in its 6-s-cis conformation. CONCLUSIONS: The methods employed here allow estimates of protein-bound ligand conformation. However, additional sites of ligand labeling will be necessary to aid in binding site localization.

PMID: 10350006 [PubMed - indexed for MEDLINE]



Source: PubMed