Structure of phytoene desaturase provides insights into herbicide binding and reaction mechanisms involved in carotene desaturation

Structure          online article

Cyanobacteria and plants synthesize carotenoids using an intricate carotene desaturation pathway. The plastid enzyme phytoene desaturase (PDS) introduces two double bonds into its membrane-bound highly lipophilic substrate, phytoene, while concomitantly isomerizing the neighbouring double bonds from trans to cis. PDS is also the target of a class of bleaching herbicides of which norflurazon is the most prominent member. The crystal structure presented here defines PDS as a member of the GR2 family of flavoproteins that attain homo-tetrameric assemblies interacting monotopically with membranes. Norflurazon binding occurs at the plastoquinone binding site and thus blocks the reoxidation of FADred. Together with the structure of the hydrophobic phytoene and plastoquinone binding tunnel, this suggests a succession of discrete catalytic events and the interaction of subunits to complete the overall reaction. A comparison with the structure of the bacterial-type carotene desaturase CRTI reveals substantial similarities in the overall protein fold, contrasted by dissimilarities in the active center structure that explain the observed differences in catalysis. Evolutionary implications are discussed.