FMN adenylyltransferase (FMNAT) is an essential enzyme catalyzing the last step of a two-step pathway converting riboflavin (vitamin B2) to FAD, the ubiquitous flavocoenzyme. A structure-based mutagenesis and steady-state kinetic analysis of yeast FMNAT unexpectedly revealed that mutant D181A had a much faster turnover rate than the wild type enzyme. Product inhibition analysis showed that wild type FMNAT is strongly inhibited by FAD, whereas D181A mutant enzyme has an attenuated product inhibition. These results provide a structural basis for the product inhibition of the enzyme and suggest that product release may be the rate-limiting step of the reaction.
[Show abstract][Hide abstract] ABSTRACT: Flavoenzymes are colourful oxidoreductases that catalyze a large variety of different types of reactions. Flavoenzymes have been extensively studied for their structural and mechanistic properties and are gaining momentum in industrial biocatalytic applications. Some of these enzymes catalyze the oxidative modification of protein substrates. New insights in oxidative flavoenzymes and in particular in novel family members point towards their potential application in the pharmaceutical, fine-chemical and food industries.
Current Opinion in Chemical Biology 05/2007; 11(2):195-202. DOI:10.1016/j.cbpa.2007.01.010 · 6.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Flavin coenzymes play a variety of roles in biological systems. This Perspective highlights the chemical versatility of flavins by reviewing research on five flavoenzymes that have been studied in our laboratory. Each of the enzymes discussed in this review [the acyl-CoA dehydrogenases (ACDs), CDP-6-deoxy-l-threo-d-glycero-4-hexulose-3-dehydrase reductase (E3), CDP-4-aceto-3,6-dideoxygalactose synthase (YerE), UDP-galactopyranose mutase (UGM), and type II isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IDI-2)] utilizes flavin in a distinct role. In particular, the catalytic mechanisms of two of these enzymes, UGM and IDI-2, may involve novel flavin chemistry.
The Journal of Organic Chemistry 09/2007; 72(17):6329-42. DOI:10.1021/jo0703092 · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The biosynthesis of one riboflavin molecule requires one molecule of GTP and two molecules of ribulose 5-phosphate. The imidazole ring of GTP is hydrolytically opened, yielding a 2,5-diaminopyrimidine that is converted to 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione by a sequence of deamination, side chain reduction, and dephosphorylation. Condensation of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione with 3,4-dihydroxy-2-butanone 4-phosphate obtained from ribulose 5-phosphate affords 6,7-dimethyl-8-ribityllumazine. Dismutation of the lumazine derivative yields riboflavin and 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, which is recycled in the biosynthetic pathway. The enzymes of the riboflavin pathway are potential targets for antibacterial agents.
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