TAILIEUCHUNG - Báo cáo khoa học: Structural basis of charge transfer complex formation by riboflavin bound to 6,7-dimethyl-8-ribityllumazine synthase

The amino acid residue tryptophan 27 of 6,7-dimethyl-8-ribityllumazine synthase of the yeastSchizosaccharomyces pombewas replacedby tyrosine. The structures of theW27Y mutant protein in complex with riboflavin, the substrate analogue 5-nitroso-6-ribitylamino-2,4(1H,3H)-pyrimidin-edione, and the product analogue 6-carboxyethyl-7-oxo-8-ribityllumazine,weredeterminedbyX-raycrystallography at resolutions of – A ˚ . Whereas the indole system of W27 forms a coplanarp-complex with riboflavin, the cor-respondingphenyl ring in theW27Ymutant establishes only peripheral contact with the heterocyclic ring system of the bound riboflavin | Eur. J. Biochem. 271 3208-3214 2004 FEBS 2004 doi Structural basis of charge transfer complex formation by riboflavin bound to 6 7-dimethyl-8-ribityllumazine synthase Michael Koch1 Constanze Breithaunt1. Stefan Gerhardt1 Ilka Haase2 Stefan Weber3 Mark Cushman4 Robert Huber1 Adelbert Bacher2 and Markus Fischer2 1Abteilung Strukturforschung Max-Planck-Institut fur Biochemie Martinsried Germany 2Lehrstuhl fur Organische Chemie und Biochemie Technische Universitat Miinchen Garching Germany 3Institut fur Experimentalphysik Freie Universităt Berlin Germany 4Department of Medicinal Chemistry and Molecular Pharmacology Purdue University West Lafayette IN USA The amino acid residue tryptophan 27 of 6 7-dimethyl-8-ribityllumazine synthase of the yeast Schizosaccharomyces pombe was replaced by tyrosine. The structures of the W27Y mutant protein in complex with riboflavin the substrate analogue 5-nitroso-6-ribitylamino-2 4 1H 3H -pyrimidin-edione and the product analogue 6-carboxyethyl-7-oxo-8-ribityllumazine were determined by X-ray crystallography at resolutions of A. Whereas the indole system of W27 forms a coplanar p-complex with riboflavin the corresponding phenyl ring in the W27Y mutant establishes only peripheral contact with the heterocyclic ring system of the bound riboflavin. These findings provide an explanation for the absence of the long wavelength shift in optical absorption spectra of riboflavin bound to the mutant enzyme. The structures of the mutants are important tools for the interpretation of the unusual physical properties of riboflavin in complex with lumazine synthase. Keywords biosynthesis of riboflavin crystallization 6 7-dimethyl-8-ribityllumazine synthase mutagenesis riboflavin binding. The biosynthesis of vitamin B2 riboflavin in eubacteria and fungi has been studied in considerable detail 1 2 . In brief GTP cyclohydrolase II affords 2 5-diamino-6-ribosylamino-4 3H -pyrimidinone. Reduction of the ribose side

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