Prenylated flavin mononucleotide (prFMN) is the only known cofactor that enables enzymatic 1,3-dipolar cycloaddition reactions. It is obtained by incubating UbiX (a prenyltransferase) with two substrates: flavin mononucleotide (FMN) and dimethylallyl monophosphate (DMAP). Even though the mechanism of prFMN biosynthesis was proposed in the literature on the basis of the obtained crystallographic structures, not every aspect of this process was answered. For instance, it was proposed, that prior to the formation of a bond between DMAP and FMN, phosphate group from DMAP should become protonated, without providing further evidence to support this idea.<br/>In this work, we will establish which of the possible protonation states of DMAP mostly promotes detachment of the phosphate group, which then enables the formation of a bond between DMAP and FMN. Moreover, we will determine which residues are most likely to provide hydrogens to alter DMAP's protonation state. It will be done by comparing energetics of considered process, basing on calculations employing Adaptive String method coupled with QM/MM models of UbiX’s complex with its ligands.

How does prenylated flavin mononucleotide biosynthesis occur? Computational study

2019 Fall National Meeting

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