(15)N{(31)P} REDOR NMR studies of the binding of phosphonate reaction intermediate analogues to Saccharomyces cerevisiae lumazine synthase.

Biochemistry
Tsyr-Yan YuJ Schaefer

Abstract

Lumazine synthase catalyzes the reaction of 5-amino-6-D-ribitylamino-2,4(1H,3H)-pyrimidinedione(1) with (S)-3,4-dihydroxybutanone 4-phosphate (2) to afford 6,7-dimethyl-8-D-ribityllumazine(3), the immediate biosynthetic precursor of riboflavin. The overall reaction implies a series of intermediates that are incompletely understood. The 15N{31P} REDOR NMR spectra of three metabolically stable phosphonate reaction intermediate analogues complexed to Saccharomyces cereVisiae lumazine synthase have been obtained at 7 and 12 T. Distances from the phosphorus atoms of the ligands to the side chain nitrogens of Lys92, His97, Arg136, and His148 have been determined. These distances were used in combination with the X-ray crystal coordinates of one of the intermediate analogues complexed with the enzyme in a series of distance-restrained molecular dynamics simulations. The resulting models indicate mobility of the Lys92 side chain, which could facilitate the exchange of inorganic phosphate eliminated from the substrate in one reaction, with the organic phosphate-containing substrate necessary for the next reaction.

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Citations

Jul 12, 2012·The Journal of Organic Chemistry·Arindam TalukdarMark Cushman
Sep 16, 2015·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Joseph A H Romaniuk, Lynette Cegelski
Mar 21, 2017·Journal of Magnetic Resonance·Alexander I GreenwoodChad M Rienstra

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