lumazine synthase and riboflavin synthase; involved in the riboflavin (vitamin B2) biosynthetic pathway
This superfamily contains lumazine synthase (6,7-dimethyl-8-ribityllumazine synthase, LS) and riboflavin synthase (RS). Both enzymes play important roles in the riboflavin biosynthetic pathway. Riboflavin is the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) which are essential cofactors for the catalysis of a wide range of redox reactions. These cofactors are also involved in many other processes involving DNA repair, circadian time-keeping, light sensing, and bioluminescence. Riboflavin is biosynthesized in plants, fungi and certain microorganisms; as animals lack the necessary enzymes to produce this vitamin, they acquire it from dietary sources. In the final steps of the riboflavin biosynthetic pathway, LS catalyzes the condensation of the 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione with 3,4-dihydroxy- 2-butanone-4-phosphate to release water, inorganic phosphate and 6,7-dimethyl-8-ribityllumazine (DMRL), and RS catalyzes a dismutation of DMRL which yields riboflavin and 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione. In the latter reaction, a four-carbon moiety is transferred between two DMRL molecules serving as donor and acceptor, respectively. Both the LS and RS catalyzed reactions are thermodynamically irreversible and can proceed in the absence of a catalyst. In bacteria and eukaryotes, there are two types of LS: type-I LS forms homo-pentamers or icosahedrally arranged dodecamers of pentamers, type-II LS forms decamers (dimers of pentamers). In archaea LSs and RSs appear to have diverged early in the evolution of archaea from a common ancestor.
Comment: The basic building block of enzymes belonging to this superfamily is a pentamer; members exhibit different quaternary assemblies between species.
Comment:Each pentamer contains 5 active sites which are located at the interfaces between adjacent monomers.
Structure:1EJB_A/B/C/D/E; Saccharomyces cerevisiae LS homopentamer binds a phosphonate intermediate analogue, 5-(6-D-ribitylamino-2,4-dihydroxypyrimidine-5-yl)-1-pentyl-phosphonic acid; contacts at 4A
Comment:the intermediate analogue mimics the hypothetical Schiff's base intermediate of the enzyme catalyzed reaction
Structure:1T13_A/B/C/D/E; Brucella abortus RibH2/type-II LS pentamer binds the substrate analogue inhibitor, 5-nitro-6-(D-ribitylamino)-2,4(1h,3h) pyrimidinedione and a phosphate ion; contacts at 4A
Comment:The bound phosphate ion may share the same binding site in the protein as the phosphate group of the substrate.
Structure:2B99_A/B/C/D/E: Methanocaldococcus jannaschii riboflavin synthase bound with substrate analog inhibitor, 6,7-dioxo-8-ribityllumazine; contacts at 4A.
Comment:Two substrate analogue molecules are bound in each active site with a topology in line with the stereochemistry of an intermediate.
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