InterPro domain: IPR036467

6,7-dimethyl-8-ribityllumazine synthase (lumazine synthase, LS), catalyzes the formation of 6,7-dimethyl-8-ribityllumazine by condensation of 5-amino-6-(D-ribitylamino)uracil with 3,4-dihydroxy-2-butanone 4-phosphate, the penultimate step in the biosynthesis of riboflavin.

The biosynthesis of one riboflavin molecule requires one molecule of GTP and two molecules of ribulose 5-phosphate as substrates. The final step in the biosynthesis of the vitamin involves the dismutation of 6,7-dimethyl-8-ribityllumazine catalyzed by riboflavin synthase (RS). The second product, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, is recycled in the biosynthetic pathway by 6,7-dimethyl-8-ribityllumazine synthase [ 1 ]. N-[2,4-dioxo-6-d-ribitylamino-1,2,3,4-tetrahydropyrimidin-5-yl]oxalamic acid derivatives inhibit riboflavin synthase [ 2 ].

This superfamily includes both lumazine synthase and riboflavin synthase. Both share sequence similarity, they appear to have diverged early in the evolution of archaea from a common ancestor.

The lumazine synthase structure is a pentamer consisting of five subunits related by 5-fold local symmetry [ 3 ]. Each subunits consists of a three layers (alpha/beta/alpha) with a parallel beta-sheet of four strands.

1. Biosynthesis of vitamin B2: Structure and mechanism of riboflavin synthase. Arch. Biochem. Biophys. 474, 252-65
2. A new series of N-[2,4-dioxo-6-d-ribitylamino-1,2,3,4-tetrahydropyrimidin-5-yl]oxalamic acid derivatives as inhibitors of lumazine synthase and riboflavin synthase: design, synthesis, biochemical evaluation, crystallography, and mechanistic implications. J. Org. Chem. 73, 2715-24
3. Crystal structure of lumazine synthase from Mycobacterium tuberculosis as a target for rational drug design: binding mode of a new class of purinetrione inhibitors. Biochemistry 44, 2746-58