The Flavocoenzymes FMN and FAD are essential cofactors for catalysis of a wide variety of redox reactions. Moreover, they are involved in numerous other physiological processes involving light sensing, bioluminescence, circadian time-keeping and DNA repair. The universal precursor of flavocoenzymes, vitamin B₂ (riboflavin), is biosynthesized by plants and many microorganisms but must be obtained from dietary sources by animals. Pathogenic eubacteria and probably pathogenic yeasts are unable to incorporate riboflavin from the environment and are therefore absolutely dependent on endogenous synthesis of the vitamin. Therefore, the enzymes of the riboflavin biosynthetic pathway represent potential anti-infective agents. The crystal structure of 3,4-dihydroxy-2-butanone 4-phosphate synthase of Candida albicans was solved by molecular replacement. The structure of this enzyme in complex with ribulose 5-phosphate uncovered a hitherto unknown conformation of the catalytically essential acidic loop. This conformation obviously occurs only in the absence of divalent cations. The phosphorylation of riboflavin to form FMN by the second substrate ATP is catalyzed by the enzyme riboflavin kinase. The crystal structure of the monofunctional enzyme of Schizosaccharomyces pombe was solved by multiple isomorphous replacement. Riboflavin kinase is suggested to form a novel family of phosphoryl transferring enzymes. The crystal structure of Schizosaccharomyces pombe riboflavin kinase reveals a novel ATP and riboflavin binding fold. Tetrahydrofolate and its derivatives are essential cofactors of one-carbon metabolism that are required for the biosynthesis of purines, thymidylate, serine and methionine in a vide variety of organisms; they are also required for the formylation of methionyl-tRNA. Whereas plants and many mircroorganisms obtain folate coenzymes by de novo synthesis, vertebrates depend on nutritional sources. Insufficient supply of the vitamin is conducive to anaemia in adults and to neural tube malformation in human embryos. The crystal structure of 7,8-dihydroneopterin aldolase (DHNA) of Arabidopsis thaliana was solved by molecular replacement. Due to structural and mechanistical differences of DHNA in comparison with class I and class II aldolases, a new aldolase class is proposed.     «

The Flavocoenzymes FMN and FAD are essential cofactors for catalysis of a wide variety of redox reactions. Moreover, they are involved in numerous other physiological processes involving light sensing, bioluminescence, circadian time-keeping and DNA repair. The universal precursor of flavocoenzymes, vitamin B₂ (riboflavin), is biosynthesized by plants and many microorganisms but must be obtained from dietary sources by animals. Pathogenic eubacteria and probably pathogenic yeasts are unable to i...     »