Investigation of the binding of fluorolumazines to the 1-MDa capsid of lumazine synthase by N-15{F-19} REDOR NMR

The N-15{F-19} REDOR NMR spectra of two fluorolumazines complexed to the 1- MDa beta(60) capsid of lumazine synthase have been obtained at 20.3 and 50. 7 MHz. Distances from CF3 groups of the ligands to six side- and main-chain nitrogens have been measured. These distances were used in combination wit h the X-ray crystal coordinates of wild-type lumazine synthase, complexed t o a related substrate ligand, in a series of distance-restrained molecular dynamics simulations. The result is a model of the binding site of lumazine synthase that has sufficient detail to predict the absolute configuration at C-7 of complexed 7-hydroxy-8-D-ribityl-6,7-bis(trifluoromethyl)-7,8-dihy dropteridine-2,4(1H,3H)-dione, a fluorinated analogue of an unstable, hypot hetical intermediate in the reactions catalyzed by both lumazine synthase a nd riboflavin synthase.