6.7- Dimethyl-8-ribityllumazine structure

Early work on flavinogenic ascomycetes by Masuda afforded a green fluorescent substance (initially designated G-compound), which was identified as 6,7-dimethyl-8-ribityllumazine that is structurally similar to riboflavin, although the benzenoid ring is missing.Subsequent work showed that the compound could be... 

It is generally assumed that the unusual CH acidity of 6,7-dimethyl-8-ribityllumazine is important for the understanding of the enzyme-catalyzed as well as the uncatalyzed reaction. Briefly, the position 7 methyl groups of 8-substituted 7-methyllumazine have pA values in the range of 8—9. " The anions are characterized by their 7-exomethylene structure. In cases where the position 8 substituent carries hydroxyl groups in the 2 or 3 position, a nucleophilic attack of C-7 of the exomethylene anion by the hydroxyl group is conducive to the formation of tricylic systems (Figure 9). 

Specifically, an alkaline aqueous solution of 6,7-dimethyl-8-ribityllumazine contains a mixture of at least five anionic species, namely the exomethylene-type anion with an open chain structure of the position 8 substituent and two diastereomers each of the 5-ring and 6-ring forms arising by intramolecular reaction of the 2 and 3 hydroxyl groups. The hypothesis of an involvement of one of the tricyclic species as intermediates in the biosynthesis of riboflavin is not supported by more recent data. The exomethylene form appears likely to be a late intermediate in the mechanism of lumazine synthase as documented by stopped flow analysis. Moreover, the exomethylene form (31) has been proposed as an early intermediate of the riboflavin synthase reaction. This is supported by the early observation that riboflavin synthase accelerates proton exchange at the position 7 methyl group. 

NMR spectroscopy of multiply C-labeled Compound ( samples (obtained by rapid quench experiments with various C-labeled samples of 6,7-dimethyl-8-ribityllumazine) revealed the pentacyclic structure 36 that is clearly an adduct of two 6,7-dimethyl-8-ribityllumazine (9) molecules (Figures 10 and 11). The optical absorption of the compound is well in line with the presence of a lumazine motif and a pyrimidine motif... 

Compound Q can be converted by riboflavin synthase into a mixture of 6,7-dimethyl-8-ribityllumazine, riboflavin, and 5-amino-6-ribitylamino-2,4(l//,3f/)-pyrimidinedione. " This is best explained by the hypothesis that Compound Q is an intermediate of the enzyme-catalyzed reaction than can undergo either a forward reaction affording riboflavin (10) and 6 or a reverse reaction affording 6,7-dimethyl-8-ribityllumazine (9) with similar reaction velocity. Moreover, it was shown by presteady-state kinetic analysis that Compound (X fulfills the criteria for a kinetically competent reaction intermediate. As described in more detail below, it can be deduced from X-ray structure data that the two lumazine components in the pentacyclic adduct 36 must be fused in cis. ... 

Up to now, this 1 MDa protein has been observed only in Bacillaceae. Computer modeling has confirmed that the central cavity of the icosahedral capsid is large enough to accommodate the riboflavin synthase trimer (Figure 16). However, there are no corresponding symmetry properties between the two modules that could suggest a potential orientation. The molecular structure is not known in closer detail. The import and export of substrates and products is also an open problem. It is hard to see how the channels in the capsid wall could allow the passage of 6,7-dimethyl-8-ribityllumazine, and, even less, of riboflavin. Dynamic fluctuations of the capsid structure have been proposed but remain speculative. 

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