LAUSR

Due to its specific physicochemical properties (fluorescence, photosensitizing and redox reactions), the vitamin B2, also called riboflavin (RF), has been generating a lot of interest in nanotechnologies and bioengineering for the last decade. RF, by targeting its RFVT transporters overexpressed in some cancers, is particularly used to functionalize nanovectors for anti-cancer drug delivery. From a physiopathological point of view, a RF deficiency has been implicated in various pathologies, including mendelian diseases. RF deficiency is mainly due to natural variants of its RFVT transporters that make them inactive and therefore prevent RF transport. The lack of structural data about RFVT is a major drawback for a better understanding of the role of the mutations in the molecular mechanism of these transporters. In this context, this work was aimed at investigating the 3D structure of RFVT3 and its interactions with RF. For this purpose, we used an in silico procedure including protein threading, docking and molecular dynamics. Our results propose that the natural variant W17R, known to be responsible for BVVL syndrome, prevents the recognition of RF by RFVT3 and thus blocks its transport. This in silico procedure could be used for elucidating the impact of pathogenic mutations of other proteins. Moreover, the identification of RF binding site will be useful for the design of RF-functionalized nanovectors.