Disease relevance of Ribitol, 1-deoxy-1-(3,4-dihydro-6,7-dimethyl-2,4-dioxo-8(2H)-pteridinyl)-

• The S41A mutant of riboflavin synthase from Escherichia coli catalyzes the formation of riboflavin from 6,7-dimethyl-8-ribityllumazine at a very low rate [1].
• Lumazine protein, a novel protein containing 6,7-dimethyl-8-ribityllumazine as a bound prosthetic group, is one of the several major proteins produced by the bioluminescent bacteria, Photobacterium phosphoreum. purification to complete homogeneity from cell extracts is achieved in six steps [2].
• We studied the incorporation of [1-13C]ribose and [1,3-13C2]glycerol into the riboflavin precursor 6,7-dimethyl-8-ribityllumazine, using a riboflavin-deficient mutant of Bacillus subtilis [3].
• Evolution of vitamin B2 biosynthesis: 6,7-dimethyl-8-ribityllumazine synthases of Brucella [4].

High impact information on Ribitol, 1-deoxy-1-(3,4-dihydro-6,7-dimethyl-2,4-dioxo-8(2H)-pteridinyl)-

• Multinuclear NMR spectroscopy, using various 13C- and 15N-labeled samples, revealed a pentacyclic structure arising by dimerization of 6,7-dimethyl-8-ribityllumazine [1].
• Quenching of presteady-state reaction mixtures with trifluoroacetic acid afforded a compound with an absorption maximum at 412 nm (pH 1.0) that can be converted to a mixture of riboflavin and 6,7-dimethyl-8-ribityllumazine by treatment with wild-type riboflavin synthase [1].
• The topology of the two bound ligands at the active site is well in line with the known stereochemistry of a pentacyclic adduct of 6,7-dimethyl-8-ribityllumazine that has been shown to serve as a kinetically competent intermediate [5].
• The dismutation of 6,7-dimethyl-8-ribityllumazine catalyzed by riboflavin synthase affords riboflavin and 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione [6].
• 6,7-Dimethyl-8-ribityllumazine synthase and the archaeal riboflavin synthase appear to have diverged early in the evolution of Archaea from a common ancestor [7].

Chemical compound and disease context of Ribitol, 1-deoxy-1-(3,4-dihydro-6,7-dimethyl-2,4-dioxo-8(2H)-pteridinyl)-

• Riboflavin synthase from Escherichia coli is a homotrimer of 23.4 kDa subunits and catalyzes the formation of one molecule each of riboflavin and 5-amino-6-ribitylamino- 2,4(1H,3H)-pyrimidinedione by the transfer of a 4-carbon moiety between two molecules of the substrate, 6,7- dimethyl-8-ribityllumazine [8].

Biological context of Ribitol, 1-deoxy-1-(3,4-dihydro-6,7-dimethyl-2,4-dioxo-8(2H)-pteridinyl)-

• Lumazine protein of Photobacterium leiognathi was expressed in a recombinant Escherichia coli host and was reconstituted with mixtures (random libraries) of 13C-labeled isotopologs of 6,7-dimethyl-8-ribityllumazine or riboflavin that had been prepared by biotransformation of [U-(13)C6]-, [1-(13)C1]-, [2-(13)C1]-, and [3-(13)C1]glucose [9].
• Heterologous expression of the putative open reading frame MJ0303 of Methanococcus jannaschii provided a recombinant protein catalysing the formation of the riboflavin precursor, 6,7-dimethyl-8-ribityllumazine, by condensation of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione and 3,4-dihydroxy-2-butanone 4-phosphate [10].
• Phosphotransferase from carrot is shown to catalyze the phosphorylation of 6,7-dimethyl-8-ribityllumazine specifically at position 5' of the ribityl side chain [11].

Associations of Ribitol, 1-deoxy-1-(3,4-dihydro-6,7-dimethyl-2,4-dioxo-8(2H)-pteridinyl)- with other chemical compounds

• The interaction of lumazine apoprotein with several trifluoromethyl analogs of 6,7-dimethyl-8-ribityllumazine was investigated by 19F NMR spectroscopy [12].
• The assay for the enzyme which catalyzes the second step, referred to here as the "reductase," involves the detection of the conversion of the product of the deaminase-catalyzed reaction to a compound which, after treatment with alkaline phosphatase, reacts with butanedione to form 6,7-dimethyl-8-ribityllumazine [13].
• The recombinant N-terminal domain forms a homodimer that can bind riboflavin, 6,7-dimethyl-8-ribityllumazine and trifluoromethyl-substituted 8-ribityllumazine derivatives as shown by absorbance, circular dichroism, and NMR spectroscopy [14].
• The enzyme catalyses the formation of 6,7-dimethyl-8-ribityllumazine from 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione and 3,4-dihydroxy- 2-butanone 4-phosphate [15].

Gene context of Ribitol, 1-deoxy-1-(3,4-dihydro-6,7-dimethyl-2,4-dioxo-8(2H)-pteridinyl)-

• Its direct biosynthetic precursor, 6,7-dimethyl-8-ribityllumazine, is synthesised by the enzyme 6,7-dimethyl-8-ribityllumazine synthase [16].
• As prerequisite for the analysis, the 1H NMR signals for the pro-R and pro-S hydrogens at C-1' of 6,7-dimethyl-8-ribityllumazine and riboflavin and its tetraacetate were assigned with the aid of synthetic stereospecifically deuteriated samples [17].
• Scatchard analysis of a fluorescence titration shows that the apoprotein possess one binding site, and at 30 degrees C the KdS (microM) are as follows: 6,7-dimethyl-8-ribityllumazine, 0.26; riboflavin, 0.53; and much more weakly bound FMN, 30 [18].

Analytical, diagnostic and therapeutic context of Ribitol, 1-deoxy-1-(3,4-dihydro-6,7-dimethyl-2,4-dioxo-8(2H)-pteridinyl)-

• Enzyme catalysis via control of activation entropy: site-directed mutagenesis of 6,7-dimethyl-8-ribityllumazine synthase [19].

References