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A structure-based model of the reaction catalyzed by lumazine synthase from Aquifex aeolicus
Södertörn University, Avdelning Naturvetenskap.
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2003 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 328, no 1, 167-182 p.Article in journal (Refereed) Published
Abstract [en]

6,7-Dimethyl-8-ribityllumazine is the biosynthetic precursor of riboflavin, which, as a coenzyme, plays a vital role in the electron transfer process for energy production in all cellular organisms. The enzymes involved in lumazine biosynthesis have been studied in considerable detail. However, the conclusive mechanism of the reaction catalyzed by lumazine synthase has remained unclear. Here, we report four crystal structures of the enzyme from the hyperthermophilic bacterium Aquifex aeolicus in complex with different inhibitor compounds. The structures were refined at resolutions of 1.72 Angstrom, 1.85 Angstrom, 2.05 Angstrom and 2.2 Angstrom, respectively. The inhibitors have been designed in order to mimic the substrate, the putative reaction intermediates and the final product. Structural comparisons of the native enzyme and the inhibitor complexes as well as the kinetic data of singlesite mutants of lumazine synthase from Bacillus subtilis showed that several highly conserved residues at the active site, namely Phe22, His88, Arg127, Lys135 and Glu138 are most likely involved in catalysis. A structural model of the catalytic process, which illustrates binding of substrates, enantiomer specificity, proton abstraction/donation, inorganic phosphate elimination, formation of the Schiff base and cyclization is proposed.

Place, publisher, year, edition, pages
2003. Vol. 328, no 1, 167-182 p.
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Biochemistry and Molecular Biology
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URN: urn:nbn:se:sh:diva-15547DOI: 10.1016/S0022-2836(03)00186-4ISI: 000182277200014OAI: oai:DiVA.org:sh-15547DiVA: diva2:504720
Available from: 2012-02-21 Created: 2012-02-21 Last updated: 2012-02-21Bibliographically approved

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Meining, Winfried
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Avdelning Naturvetenskap
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